Dibenzofuran and dibenzothiophene acetic acid derivatives

ABSTRACT

Dibenzofuran and dibenzothiophene derivatives of the formula   WHEREIN R1 is COOH, CHO, or CH2OH, R2 is H or alkyl of 1-4 carbon atoms, R3 is H, alkyl, alkoxy, alkanoyl, monoalkylamino, dialkylamino, or acylamino of up to 4 carbon atoms, F, Cl, Br, I, OH, NH2, NO2, CN, or CF3; and Y is O or S, with the proviso that at least one of R2 and R3 is other than H, and the physiologically acceptable salts thereof, possess antiinflammatory activity.

United States Patent 1191 Gante et a1.

[ DIBENZOFURAN AND DIBENZOTHIOPI-IENE ACETIC ACID DERIVATIVES [75]lnventors: Joachim Gante; Werner Mehrhof;

Albrecht Wild, all of Darmstadt, Germany [73] Assignee: Merck PatentGesellschaft mit beschrankter Haftung, Darmstadt, Germany 22 Filed: May10, 1973 211 Appl. No.: 358,872

[30] Foreign ApplicationPriority Data May 13, 1972 Germany 2223391 Dec.16, 1972 Germany 2261745 {56] References Cited UNITED STATES PATENTS4/1970 Wang 260/3462 3/1971 Cavalleri...

4/1972 Shen 260/3462 OTHER PUBLICATIONS Gilman, 1, CA 49:6218 (1955).

1451 July 29,1975

126111161, CA 51:5076-5077 1957 Chatterjea, CA 52:3759-3761 (1958).Gilman, 11, CA 411752453 1947 Hogg, CA 40:4716-4717 (1946). Gilman, 111,CA 34:2366 2367 1940 Burger, CA 34:1654-1655 (1940). Giiman, IV, CA33:579-581 (1939).

Primary Examiner-John M. Ford Assistant Examiner-C. M. S. JaisleAttorney, Agent, or Firm-Millen, Raptes 8:. White [57] ABSTRACTDibenzofuran and dibenzothiophene derivatives of the formula CHR Rwherein R is COOH, CI-IO, or CH Ol-l, R is H or alkyl of 1-4 carbonatoms, R is H, alkyl, alkoxy, a1- kanoyl, monoalkylamino, dialkylamino,or acylamino of up to 4 carbon atoms, F, Cl, Br, I, OH, N11 N0 CN, or C1and Y is O or S, with the proviso that at least one of R and R is otherthan H, and the physiologically acceptable salts thereof, possessantiinflammatory activity.

27 Claims, N0 Drawings 1 DIBENZOFURAN AND DIBENZOTHIOPHENE ACETIC ACIDDERIVATIVES BACKGROUND OF THE INVENTION This invention relates to noveldibenzofuran and dibenzothiophene derivatives similar to the known 2-dibenzofurylacetic acid (cf. J. Amer. Chem. Soc. 68.

SUMMARY OF THE INVENTION The novel compounds of this invention arediben- .zofuran and dibenzothiophene derivatives of the general FormulaI z-caa a (I) in which Z is DETAILED DISCUSSION.

Compounds of Formula I possess, with good compatibility, excellentantiphlogistic activity. In particular, they exert a favorable influenceon chronically progressive inflammation diseases involving the joints.They also possess analgesic and antipyretic activity. Therefore, thecompounds of Formula I can be employed as drugs, especially forproducing antiphlogistic, i.e., antiinflammatory, effects in livingbeings. They are also useful as intermediates for the preparation ofother medicines. In its composition aspect, this invention relates topharmaceutical compositions comprising a compound of Formula I inadmixture with a pharmaceutically acceptable carrier. In its method ofuse aspect, this invention relates to the treatment of inflammatoryconditions with a compound of Formula I.

In its preferred aspects, this invention relates to the compounds ofFormulae Ia Ik below, and pharmaceutical compositions comprising themwherein any groups not otherwise defined have the values given inFormula I. la R is a free or esterified carboxyl group of l-20 carbonatoms, optionally monoor disubstituted CONI-I group, CN, or R wherein R,is CHO, CHOH-SO M CHOH-OA,

CH(OA) -Cl-I(OAc) CHOHSA, CH- (SA) -CH=NOH, -CH OH, CH OAc, Cl-l- OA, or=CHOA, =CHOAc or =CHOAr,

M is an equivalent of an alkali or alkaline earth metal,

A is alkyl of l-8, preferably 1-4 carbon atoms, e.g.,

methyl, ethyl, propyl, isopropyl, butyl, isobutyl, octyl, or, when two Agroups are present, collectively .alkylene of 2-5 carbon atoms,optionally interrupted by O, e.g., ethylene, propylene, trimethylene,ethyleneoxyethylene;

Ac is acyl of 1-18, preferably alkanoyl of 2-10, alkyl- :sulfonyl of1-6, arylsulfonyl of 6-10, or aroyl of 3 -10 carbon atoms, and

Ar is aryl of a total of 6-10 carbon atoms, optionally substituted,e.g., by R R is COOR CONHR CON(A) CHO, or

CHgOH, wherein R is H or an alkyl, cycloalkyl, cycloalkylalkyl, aryl, oraralkyl, respecively up to 20 carbon atoms which optionally can contain1 or 2 C-C multiple bonds and/or whose carbon chain can be interruptedonce or several times by O and/or can be branched and/or can be monoorpoly-substituted by C1, OH, SH, and/or NH Q being 0, S, NH, oroptionally OH-substituted N- alkyl or l-6 carbon atoms, N-Ar, orN-aralkyl of 7-10 carbon atoms;

R is COOR CHO, or CH OH, wherein R is H, A, or dialkylaminoalkyl of upto 10 carbon atoms;

Id R is COOH, COOCI-I or COOC H Ie R is CH or C H especially those of IaId;

If R is CH especially those of la Id;

lg R is H, CH C l-I C11 0, CH CO, F, Cl, Br, I,

OH, NH or N0 especially those of la Id;

Ih R is H, especially those of la Id;

Ii R is COOH, COOA, CHO, or CH OH,

R is CH and R is H, C H F, Cl, Br, or I",

R, is COOH, COOA, CHO, or CH OH,

R is CH and R is H or F;

Ik R is COOH or COOA,

R is CH and R is H or 7-F.

Included in the compounds of Formula I and la are functional derivativesof aldehydes (R functionally modified Cl-lO-group) derived from the enolform thereof and accordingly exhibiting an additional double bond, thushaving the formula ZCR =R for example, the enol ethers (R, ==CHOA or=43HOAr, respectively) and the enol esters (R =CHOAc).

R is preferably at the 3-, 7-, or 8-position. However, this group canalso be at the 1-, 4-, 6-, or 9-position. (The numbering of theindividual positions is in accordance with the disclosure in The RingIndex, Second Edition, 1960, No. 3011.)

Examples of compounds of Ia wherein R is an esterified carboxyl groupare those wherein the esterifying group is hydrocarbon including alkyl,arylalkyl, e.g., benzyl, p-methylbenzyl, phenethyl, aryl, e.g., phenyl;and wherein R is monoor disubstituted CONH are CONHA and CONA wherein Ais as defined above, or cycloalkyl or cycloalkyl alkyl of 3-7 rings anda total of 3-12 carbon atoms, e.g., cyclopentyl, e.g., cyclohexyl,cyclopentylmethyl, ethyl and propyl, aryl, e.g., carbocyclic containing1-3 separate or fused rings, and the corresponding aralkyl wherein thearyl portion is as defined herein and the alkyl portion contains 1-4carbon atoms.

Aryl preferably in each instance is of 6-10 ring carbon atoms and morepreferably is carbocyclic, e.g., phenyl, biphenyl and naphthyl,optionally substituted by R In its process aspect, this inventionrelates to a process for the preparation of compounds of general FormulaI, which comprises converting, in a compound of general Formula IIwherein X is a group convertible into the group CHR R and Z, R R R and Yhave the values indicated in Formula I, X into the group -CHR R ortreating a compound of general FormulaIII W CHR R (I I I CHRR A W l 2CHR R wherein one of the two G groups is OH or a diazonium salt group,and the other is H, and one of the two benzene rings is substituted byR;,, and R R R and Y have the values given in Formula I; and optionallythereafter converting, in a thus-obtained product of Formula I, in oneor several stages, one or both of the R and/or R groups into one or twoother R and/or R groups having a different value.

In all of the above formulae, R preferably is a free COOH, CHO or CH OHgroup. However, such groups can also be a functionally modified group.The term functionally modified group as used herein means a group thatcan be removed in vivo to regenerate the free group. Examples areesterified COOH- groups, wherein the alcohol portion is preferably ofl-l 4 carbon atoms, a free or acetalyzed CHO group or a free oresterified CH OH group, e.g., as defined in la. Because the freecarboxylic acids, aldehydes, and alcohols, of Formula I (R COOH, CHOand/or CH OH) are physiologically active compounds, it will be obviousthat functional derivatives thereof which can be converted, e.g.,hydrolyzed, thereto under physiological, i.e., in vivo, conditions,preferably at a pH of between 1 and 8, are the functional equivalentsthereof. Therefore, the type of functional modification of the group Ris not critical, so long as it is removable under physiologicalconditions to the free acid, aldehyde or alcohol and is physiologicallyacceptable. Of course, it is also possible to modify the physiologicaleffects obtained with the free forms by a suitable selection of thefunctional group, for example, depot effects can be achieved by the useof long-chain or difficult-tosaponify alcohol groups or acyl groups inesters. Improvements in solubility can be acheived by the incorporationof polar groups (O-atoms, N-atoms) into such functionally modified Rgroups.

For example, R, can be COOR or COOR as defined above, preferably COOH,COOCH or COOC H R is preferably hydrogen; alkyl of 1-20, preferably 1-8,more preferably l-4, carbon atoms, e.g., methyl, ethyl, n-proply,isopropyl, n-butyl, isobutyl, sec.-butyl, tert.-butyl, npentyl, isoamyl,n-hexyl, n-heptyl, n-octyl, 2-ethylhexyl, n-nonyl, n-decyl, n-undecyl,n-dodecyl, n-tridecyl, n-tetradecyl; alkenyl of 2-8, preferably 2-4,carbon atoms, e.g., vinyl, allyl, crotyl; alkinyl of 2-8, preferably2-4-carbon atoms, e.g., propargyl; hydroxyalkyl of 2-8, preferably 2-4,carbon atoms, wherein the hydroxy group is preferably [3 or w, e.g., 2-

hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl; alkoxyalkyl, wherein thealkoxy group is of l-S, preferably l-4, carbon atoms and alkyl is asdefined above, e.g., 2-methoxyethyl, 2-ethoxyethyl; 3-oxa-5-hydroxypentyl, 3-oxa-5-methoxypentyl, 3-oxa-5- butoxyphenyl,3,6-dioxa-8-hydroxyoctyl, 3,6-dioxa-8- methoxyoctyl,3,6-dioxa-8-ethoxyoctyl, 3-oxa-5- ethoxypentyl; aminoalkyl,alkylaminoalkyl and dialkylaminoalkyl wherein alkyl. in each instancecontains up to 8, preferably up to 4 carbon atoms, e.g., 2- aminoethyl,3-aminopropyl, Z-dimethylaminoethyl, 2- diethylaminoethyl,2-di-n-propylaminoethyl, 3- dimethylaminopropyl, 3-diethylaminopropyl,2- methyl-3-diethylaminopropyl; 4-dimethylaminobutyl,4-diethylaminobutyl; cycloalkyl, preferably containing 5-8 ring carbonatoms, and l-3 rings, e.g., cyclopentyl, cyclohexyl; cycloalkylalkyl,wherein cycloalkyl and alkyl are as defined above, e.g.,2-cyclohexylethyl, 3- cyclohexylpropyl; azacycloalkyl, e.g., N-methylpiperidyl(4); azacycloalkylalkyl and related cycloarnino groups,e.g., containing in a total of 5-7 ring atoms and a ring N, O, or S atomB- to the amino group, e.g., (N-methylpiperidyl-3)-methyl,2-(N-methylpiperidyl-2)-ethyl, 2-pyrrolidinoethyl, Z-piperidinoethyl, 2-homopiperidinoethyl, 2-morpholinoethyl, 2-thiomorpholinoethyl,2-(N-methylpiperazino)-ethyl, 2-(N- ethylpiperazino)-ethyl,Z-(N-phenylpiperazino)-ethyl,

2-(N-2-hydroxyethylpiperazino )-ethyl, 2-( N-methylhomopiperazino)-ethyl, 2-(N- benzylpiperazino)-ethyl,2-pyrrolidinopropyl, 3- pyrrolidinopropyl, 2-piperidinopropyl, 3-

piperidinopropyl, 2-(N-methylpiperazino)-propyl, 3- (N-methylpiperazino)-propyl, 3-( N-ethylpiperazino propyl, 3-(N-phenylpiperazino)-propyl,2- morpholinopropyl, 3-morpholinopropyl, 3-thiomorpholinopropyl,2-methyl-3-pyrrolidinopropyl, 2-methyl-S-piperidinopropyl, 2-methyl-3-morpholinopropyl; mercaptoalkyl, e.g., Z-mercaptoethyl;alkylmercaptoalkyl, e.g., 2-methylmercaptoethyl, 2-ethylmercaptoethyl,S-methylmercaptopropyl, 3-ethylmercaptopropyl; aryl as defined above,e.g., phenyl, o-tolyl, m-tolyl, p-tolyl, p-ethylphenyl, lnaphthyl,Z-naphthyl; aralkyl, e.g., benzyl, p-

methylbenzyl, l-phenylethyl, 2-phenylethyl. R can also be Z-CHR Cl-lwherein Z is as defined above.

R, can also represent other functionally modified carboxyl groups.Examples are acid halogenides (R COF, COCl, COBr); ortho esters (R C(OA)acid anhydrides (R COOAcyl, wherein Acyl is the acyl group of acarboxylic acid of up to 28 carbon atoms, e.g., as defined herein above,preferably the residue Z-CHR CO-); nitriles (R CN); acid amides (R CONHCONHA, CON(A) or CONHAr); hydroxamic acids (R CONHOH); acid hydrazides(R CONHNH or CONHNHA); acid azides (R CON imino ethers (R C(OA)=NH);acid amidines (R, C(=Nl-l)Nl-l acid hydrazidines (R, C( Nl-I )=NNH orC(NHNH )=NH); thio acids (R CSOl-l or COSl-l); thio acid esters (R CSOAor COSA); and thio acid amides (R CSHN CSNHA, or CSN(A) wherein the Agroups, which can be the same or different when more than one ispresent, have the values given above.

Examples of the preferred substituted amides groups areN-monoalkylamides, -dibenzofuryl)-propionamide methylamides,ethylamides, n-propylamides, isopropylamides, n-butylamides,isobutylamides; N,N- dialkylamides, e.g., dimethylamides,methylethylamides, diethylamides, di-n-propylamides, diisopropylamides,di-n-butylamides, diisobutylamides; N- monoaryland N-monoaralkylamides,e.g., anilides, N- benzylamides; N-hydroxyalkylamides, e.g., N-2-hydroxyethylamides; N,N-bis-hydroxyalkyl-amides, e.g.,N,N-bis-2-hydroxyethylamides; heterocyclic amides, e.g., pyrrolidides,piperidides, morpholides, thiomorpholides, piperazides,N'-alkyl-piperazides, e.g., N'-methylpiperazides, N'-ethylpiperazides,N-hydroxyalkyl-piperizides, e.g., N'-2-hydroxyethylpiperazides.

The compounds of Formula I include aldehydes of the formula ZCHR CHO,and also derived therefrom, the metal, particularly the alkali metaland/or alkaline earth metal bisulfite, especially sodium bisulfite,addition compounds of the formula Z-CHR CHOH-SO M hemiacetals of theformula Z-CH- R -CHOHOA, acetals of the formula Z--CH- R -CH(OA)acylates of the formula Z-CHR CH- (OAc) hemimercaptals of the formulaZCHR CHOA-SA, mercaptals of the formula Z-CI-l- R --Cl-l(SA) oximes ofthe formula Z--CHR CH- =NOH, enol ethers of the formula Z-CR =CHOA orZCR =CHOAr, enol esters of the formula or unsaturated aliphatic,cycloaliphatic, aromatic, or heterocyclic substituted or unsubstitutedcarboxylic acid or sulfonic acid. Preferred carboxylic acids are fattyacids of l-18, preferably 1-6, carbon atoms, e.g, formic acid, aceticacid, propionic acid, butyric acid, isobutyric acid, valeric acid,isovaleric acid, caproic acid, isocaproic acid, enanthic acid, caprylicacid, pelargonic acid, capric acid, lauric acid, myristic acid, palmiticacid, stearic acid. Others are crotonic acid, oleic acid,cyclohexanecarboxylic acid, cyclohexylacetic and -propionic acid,benzoic acid, phenylacetic and -propionic acid, picolinic acid,nicotinic acid, isonicotinic acid and furan-2-carboxylic acid. Ofspecial importance are those esters which contain a group rendering thecompound water-soluble, e.g., a carboxyl, hydroxyl, or amino group,since they can be used particularly in the form of their ester salts ofthe preparation of aqueous solutions. The thus-obtainable monoestersand/or dydroxy or amino esters are derived, for example, fromdicarboxylic acids, e.g., oxalic, malonic, succinic, maleic, glutaric,dimethylglutaric, adipic, pimelic, acetonedicarboxylic, phthalic,tetrahydrophthalic, hexahydrophthalic, or diglycolic acid,hydroxycarboxylic acids, such as glycolic acid, or aminocarboxylicacids, such as diethylaminoacetic acid or aspartic acid. Preferredsulfonic acid esters are those derived from alkylsulfonic acids of 1-6carbon atoms, e.g., methaneand ethanesulfonic acid and arylsulfonicacids of 6-10 carbon atoms, e.g., benzene-, p-toluene and 1- andZ-naphthalenesulfonic acids. The Ol-l-group in Formula I (R CH OH) canalso be esterified with an inorganic acid, such as sulfuric acid orphosphoric acid, and can also represent an ester salt (e.g., sodiumsalt) group derived from such an ester.

R can also represent an etherified ClhOH-group, preferably alkoxy ofl-12, preferably 1-4 carbon atoms, e.g., methoxy, ethoxy, propoxy,isopropoxy, nbutoxy, isobutoxy, sec.-butoxy, or tert.-butoxy, as well asamyloxy, isoamyloxy, n-heptyloxy, n-hexyloxy, noctyloxy, n-decyloxy,n-dodecyloxy. Examples of other etherified groups are alkenyloxy oralkinyloxy of preferably up to 12, especially up to 4 carbon atoms,e.g., vinyloxy, allyloxy, propargyloxy, or butenyloxy, aryloxy ofpreferably 6-12 carbon atoms, e.g., phenoxy, 0-, mor p-tolyloxy, 1- and2-naphthyloxy, and aralkoxy of preferably 7-12 carbon atoms, e.g.,benzyloxy, pmethylbenzyloxy, land 2-phenylethoxy and land 2-naphthylmethoxy. These alkoxy, alkenyloxy, alkinyloxy, aryloxy andaralkoxy groups can be unsubstituted or monoor polysubstituted,especially by hy- ZCR =CHOAc, and Schiff bases of the formulaZ-Cl-ldroxy, lower alkoxy of l-4carbon atoms, e.g., methoxy,

R -CH=NAr, hydrazones of the formula ZCI-l- R CH=NNH-R' wherein Rpreferably is H, Ar, CONl-l CONHAr, COOA, CSNl-l or the residue of aGirard reagent) and azines of the formula Z-CH- R CH=N--N=CHCHR Z,wherein in each instance Z,M A, Ac, Ar and R have the values givenabove.

These functional derivatives, among which the bisulfite compounds andthe acetals are preferred, are normally more stable than the freealdehydes, which are in most cases very reactive, and thus can be morereadily processed into stable pharmaceutical preparations than the freealdehydes.

Among the compounds of Formula I are those wherein R is CH OH. Here,also the OH-group can be functionally modified, e.g., esterified with asaturated ethoxy or n-butoxy, halogen, e.g., F, Cl, Br or I, amino,substituted amino, e.g., monoalkylamino or dialkylamino, wherein thealkyl groups contain preferably 1-4 carbon atoms, heterocyclic groups,e.g., pyrrolidino, piperidino, homopiperidino, morpholino,thiomorpholino, N-alkylpiperazino, wherein the alkyl group contains l-4carbon atoms, N-phenylpiperazino, N-(hydroxyalkyl)-piperazino, mercaptoand alkylmercapto of 1-4 carbon atoms.

A preferably is methyl or ethyl but can also be, for example,, propyl,isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-amyl, isoamyl,hexyl, isohexyl, heptyl, isoheptyl, octyl and isooctyl.

In the acetals, hemi-mercaptals, mercaptals, acid amides and thio acidamides of Formula 1, in which two A groups are present in the formula,the two A groups can 7 )CH(CH collectively be, for example, CH 2):: 2)4-2)sr 2 H -OCH CH and, less preferably CH CI-l(CH CH(CH )-CH(Cl-l and CHCH(C H In the compounds described above having an Ac group, Acpreferably is acetyl, or less preferably propionyl, butyryl orisobutyryl. Ac can also be, for example, formyl, valeryl, isovaleryl,caproyl, trimethylacetyl, heptanoyl, octanoyl, decanoyl,methanesulfonyl, hexanesulfonyl, benzenesulfonyl, p-toluenesulfonyl, lorZ-naphthalenesulfonyl, benzoyl, toluyl and lor 2- naphthoyl.

Ar is preferably phenyl, but can also be phenyl substituted by 1-3substituents, e.g., methyl, ethyl, methoxy, ethoxy, F, Cl, Br, forexample 0-, mand especially ptolyl, o-, mand p-ethylphenyl, o-, mandpmethoxyphenyl, o-, mand p-ethoxyphenyl, o, mand p-fluorophenyl, o-,mand p-chlorophenyl, o-, mand p-bromophenyl and land Z-naphthyl.

M preferably is Na, but can also be, for example, K or an equivalent ofCa or Mg.

R preferably contains 1-3 carbon atoms and, in particular, is CH;, and CH and when R is other than H, also H.

R preferably is H or F and can also be, for example, methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec.-butyl, tert.-butyl,methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy,sec.-butoxy, tert.- butoxy, formyl, acetyl, butyryl, isobutyryl,methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino,isobutylamino, sec.-

butylamino, tert.-butylamino, dimethylamino, methylethylamino,diethylamino, formamido, acetamido, propionamido, butyramido,isobutyramido, Cl, Br, I, OH, NH N0 CN and CF R preferably a 7- or8-position substituent.

The dibenzofuran and dibenzothiophene derivatives of Formulae I andla-Ik can be produced by:

a. i. reacting a compound of the Formula llaa (II, X H or M), wherein Mis MgHal or an equivalent of a metallic atom or an organometallic groupand Hal is Cl, Br, or I, with a compound of Formula Vla.

Vla wherein X, is Hal or an hydroxy or amino group, which optionally canbe in reactively functionally modified form, or with a des-HX derivativethereof, or

ii. reacting a compound of the Formula IIab (II, X X with a compound ofthe formula M-CHR R (VIb), or

iii. reacting a compound of the Formula lIac (II, X CHR M) with acompound of the formula X R (Vlc) or with a des-HX, derivative thereof,or

iv. reacting a compound of the Formula Ilad (II, X -CHR X or a des-HX,derivative thereof with a compound of the formula MR (VId), or

v. reacting a compound of the Formula Ilae (ll, X --CHR M) with acompound of the formula X R (VIe) or with a des-HX derivative thereof,or

vi. reacting a compound of the Formula IIaf (II, X -CHR X or a des-HXderivative thereof with a compound of the formula MR (Vlf), underconditions wherein HX, and/or MX, are split off; or

b. treating a compound of the Formula Ilb (II, X X wherein X is a groupoxidizable to the group CHR R and preferably is a group otherwisecorresponding to -CHR R but which contains in place of R 21 groupoxidizable to R with a dehydrogenating and/or oxidizing agent; or

c. treating a compound of the Formula He (II, X X wherein X is a groupreducible to the group CHR R and preferably is a group otherwisecorresponding to CHR R but additionally contains at least one reduciblegroup and/or multiple bond, with a reducing agent; or

d. treating a compound of the Formula lid (ll, X X,) wherein X,otherwise corresponds to the group -CHR,R but additionally contains agroup removable by thermolysis or solvolysis, with a thermolyzing orsolvolyzing agent; or

e. reacting a compound of the Formula He (II, X CHR X or a des-HXderivative thereof, with CO and/or a metal carbonly, optionally in thepresence of a reducing agent and/or a reaction catalyst; or

f. treating a halogenide of the Formula llf (II, X CO--CHR Hal) with astrong base; or

g. rearranging a compound of the Formula Ilg (II, X CHR -X wherein X is-CO--R or C(- =NOH)-R with HN or an acidic catalyst, respectively; or

b. catalytically or thermally splitting an epoxide of the Formula IIh(II, X -CR7-CHR wherein one of R and R is R and the other is H; or

i. treating a compound of the Formula lli (II, X -CR-,X CHR OR wherein Ris H, A, or Ac, with an agent which splits off HX or j. reacting acompound of the Formula Ilj (II, X -CO-R with a compound of the FormulaVII Ar P=CHOR 1 (VII) R is A or Ar; or

k. reacting a compound of the Formula Ilk (ll, X -CHR CH X wherein X.;is Hal or a diazonium group, with a compound of the Formula R OH and/orArOH or with a metallic derivative of such a compound; or

1. reacting a compound of the Formula III (II, X -COCH with ammoniumpolysulfide or with a primary or secondary amine in the presence ofsulfur.

The above-mentioned Formulae Ilaa llaf, as well as IIb III, allcorrespond to Formula II, except X in each case has the values given forthe individual formula.

In the aforementioned compounds, in addition to MgCl, MgBr, or MgI, Mcan especially be an equivalent of an alkali metal atom (e.g., Li, Na,K), an alkaline earth metal atom (e.g., Mg, Ca), or a Cu, Cd or Zn atom,or an organometallic radical, e.g., Mg-Z, Cd-Z, or Zn-Z. The termorganometallic residue" includes organoboron groups, for example, 9-borabicyclo[3,3,l]nonyl-(9). When X optionally is a hydroxy or aminogroup in reactively functionally modified form, included especially arethose groups which can be split off, under the selected reactionconditions, in a manner analogously to Cl, Br, or I, as Hx for exampleNH NHA, NHAr, OH, ASO (e.g., methanesulfonyloxy), ArSO O-- (e.g.,benzenesulfonyloxy, ptoluenesulfonyloxy, 1- orZ-naphthalenesulfonyloxy), AcO (e.g., acetoxy, benzoyloxy), or anetherified OI-lgroup of preferably 1-7 carbon atoms (e.g., methoxy,benzyloxy).

The individual variants of the process are more specifically describedas follows:

a. Compounds of Formula I can be obtained, for example, by the reactionof dibenzofurans and/or -thiophenes (ll, X H), optionally substituted inthe 2- position, with compounds (Vla) wherein X, preferably is C1 or Br,under Friedel-Crafts alkylation conditions. Especially suitable as thestarting compounds are, on the one hand, dibenzofuran, dibenzothiophene,2- alkyldibenzofurans, such as Z-methyldibenzofuran,2-alkyl-dibenzothiophenes, e.g., 2-methyldibenzothiophene,2-alkoxy-dibenzofurans, e.g., 2- methoxydibenzofuran,2-alkoxy-dibenzothiophenes, e.g., Z-methoxydibenzothiophene and, on theother hand, 2-halocarboxylic acids of the formula R -Cl-ll-lal- COOl-l,e.g., 2-chloro and Z-bromopropionic acid and the functional derivativesthereof, e.g., the corresponding esters, nitriles and amides; and also2-haloalcohols of the formula R -Cl-ll-lal-Cll ol-l, e.g., 2-chloro-andby Z-bromopropanol and/or esters and ethers thereof. Also suitable arethe des-HX derivatives of the compounds of Formula Vla, for example, thecorresponding unsaturated compounds, e.g., allyl alcohol and/or estersand ethers thereof, or epoxides, e.g., propylene oxide. The reactiontakes place generally according to procedures disclosed in theliterature. Examples of suitable catalysts are Lewis acids, e.g., AlClAlBr BF and the etherate of the latter, BCl BBr ZnCl ZnBr FeCl SbCl amineral acid, e.g., HF, H 50 H,,PO,, or an anhydride thereof, e.g., PPreferably, an inert solvent is employed, e.g., hexane,1,2-dichloroethane, 1,1,2-trichloroethane, trichloroethylene, CS ornitrobenzene. Normally, the reaction is first conducted with cooling andterminated at a temperature of about 0 to 100 C., suitably at roomtemperature. Reaction times of about 1 hour to 100 hours are usuallyrequired.

A variant of this method comprises heating a compound of Formula II (XH) with a halofatty acid to a temperature of about 100-250 C., in thepresence of a heavy metal oxide, e.g., Fe O and a metallic halide, e.g.,KBr.

Compounds of Formula I can also be obtained by the reaction of anorganometallic compound of Formula Ilaa (X M), VIb, IIac, VId, IIae orVIf, respectively, with a halogen compound or an analog thereof of Formula Vla, llab, Vlc, Ilad, VIe or Ilaf, respectively, or with thecorresponding des-HX, derivative, especially the dehydrohalogenderivative thereof, under conditions wherein MX, is split off and whichcorrespond to the conditions for organometallic syntheses known in theliterature.

Starting compounds for this reaction are, for example:

Z-M (llaa, X M): 2-dibenzofuryllithium, 2-dibenzofurylmagnesiumchloride, bromide and iodide, bis( Z-dibenzofuryl )cadmium,2-dibenzothienyllithium, 2-dibenzothienylmagnesium chloride, bro- 6 of2-dibenzofurylacetic acid, 2- dibenzofurylacetaldehyde, 2-(2-dibenzofuryl ethanol, Z-dibenzothienylacetic acid, 2-

dibenzothienylacetaldehyde, or 2-(2- dibenzothienyl)-ethanol and/or thefunctional derivatives thereof;

Z-CHR X (llad): derivatives of the above-named compounds halogenated inthe a-position, e.g., 2- dibenzofurylchloro-, -bromo-, or -iodoaceticacid, 2-dibenzothienylchloro-, -bromo-, and -iodoacetic acid, and thefunctional derivatives thereof, and derivatives of2-dibenzofurylbromoethanol and of 2-dibenzothienylbromoethanol, 2-(2-dibenzofuryl)-2-bromoethanol and 2-(2- dibenzothienyl)-2-bromoethanoland the ethers and esters thereof;

ZCHR M (llae l-( 2-dibenzofuryl)-ethyllithium -magnesium chloride or-magnesium bromide, 1- (2-dibenzothienyl)-ethyllithium, -magnesiumchloride, and magnesium bromide;

ZCHR X (Ilaf): 2-( 1-chloroethyl)-dibenzofuran,

2-( l-bromoethyl)-dibenzofuran, 2-( l-hydroxyethyl)-dibenzofuran,2-vinyldibenzofuran, 2-(1- chloroethyl)-dibenzothiophene, 2-(l-bromoethyl dibenzothiophene, 2-( l-hydroxyethyl)-dibenzothiophene,2-vinyldibenzothiophene;

X,CHR,R (VIa): 2-halocarboxylic acids, 2- haloalkanals, 2-haloalkanolsand the functional derivatives thereof, preferably the bromine andiodine compounds, e.g., 2-chloropropionic acid, 2- bromopropionic acidethyl ester, 2- bromopropionitrile, 2-bromopropionaldehydediethylacetal, 2-chloropropanol, 2- bromopropylmethyl ether, and thedes-HX, derivatives of these compounds, e.g., propylene oxide, allylalcohol;

MCHR R (Vib): the Grignard compounds and organolithium compounds derivedfrom 2- halocarboxylic acids and/or the salts and functional derivativesthereof, from 2-haloaldehyde derivatives, or from 2-haloalcoholderivatives, e.g., the lithium salt of 2-lithiumpropionic acid;

X,R (Vlc): alkyl halides, e.g., methyl chloride, bromide, or iodide,ethyl chloride, bromide or iodide, n-propyl chloride, bromide or iodide,n-butyl chloride, bromide or iodide, and also the corresponding alcoholsand the reactive esters thereof, e.g., the sulfuric acid and sulfonicacid esters, e.g., the p-toluenesulfonates, e.g., dimethyl sulfate andp-toluenesulfonic acid ethyl ester;

MR (Vld): the Grignard and organolithium compounds derived from theaforementioned halides Vlc, e.g., methyllithium, methylmagnesiumchloride, bromide or iodide, butyllithium;

X R (VIe): carbonic acid derivatives, e.g., orthocarbonic acidtetraethyl ester, CO diethyl carbonate, ethyl chloroformate; formic acidderivatives, e.g., ethyl forrnate, ethyl orthoformate; derivatives offormaldehyde, e.g., methylal, chloromethyl methyl ether; bromomethylbenzyl ether;

MR (Vlf): salts of hydrocyanic acid, e.g., NaCN,

KCN; Cu (CN) These starting compounds for the most part are known or canbe prepared in a conventional manner. Thus, the halogen compounds areobtained, for example, by the direct halogenation of the halogen-freebasic members, or by reacting the corresponding hydroxy compounds withSOCl HBr or PBr The iodine compounds can also be produced, for example,by reaction of the bromine compounds with XI. The organometalliccompounds can be obtained, for example, by metallizing the correspondinghydrogen or halogen compounds, e.g., with metallic Na, Li, or Mg, Nal-l,NaNl-l alkyllithium or aryllithium compounds, e.g., butyllithium orphenyllithium.

Suitable solvents for these reactions are, for example, ethers, e.g.,diethyl ether, diisopropyl ether, 1,2- dimethoxyethane, tetrahydrofuran(THF), dioxane and mixtures thereof with each other or withhydrocarbons, e.g., hexane, benzene, toluene or xylene, amides, e.g.,dimethylformamide (DMF), hexamethylphosphoric acid triamide, sulfoxides,e.g., dimethyl sulfoxide (DMSO). The reaction temperatures are normallyabout -20 to 180 C., preferably to 70 C. The reaction times usuallyrange from 0.5 to 72 hours. It is possible to add a Lewis acid to thereaction mixtures, e.g., AlCl FeCl ZnCI Furthermore, the reaction can bestarted in a low-boiling solvent, e.g., diethyl ether, and this solventthen replaced by a higher boiling one, e.g., benzene, and the reactioncan then be terminated in the latter solvent, for example by refluxing.

Several variants of these organometallic reactions are specifically:

Carboxylic acids of Formula I (R, COOH) are obtained by reacting acompound Ilae with CO For this purpose, a dry stream of CO can beintroduced into the cooled solution of the organometallic compound, orthis solution can be poured onto solid CO Preferably, Grignard compoundsof the formula Z-CH- R- .MgHal are employed, which can be produced witha large excess of a mixture of magnesium filings and pulverizedmagnesium, and a vigorous steam of CO is passed through the reactionmixture during the Grignardization.

In addition to employing an organometallic compound of Formula Ilaa,there can also be employed compounds of Formulae Vlb, IIac, VId, IIaeand/or Vif, wherein M is an organoboron residue, particularly 9-borabicyclo[3,3,1 ]nonyl-(9). These starting compounds can be obtained,for example, by reacting the corresponding organolithium compounds with9- borabicyclo[3,3,l ]nonane in an ether at a temperature of about l 0to +20 C. and subsequent acidification. They normally are not isolated.The actual reaction of these organoboron compounds with the compounds ofFormula Vla or of Formulae Ilab, Vlc, IIad, Vle and/or Ilaf, takes placesuitably with the addition of a lower tert.-alkanol and an excess of alower alkali metal tert.- alkoxide, preferably potassium tert.-butylateor -pentylate, at a temperature of about -10 to C.

Aldehydes and/or the derivatives thereof of Formula I (R, optionallyfunctionally modified aldehyde group) can be obtained by reacting theorganometallic compounds of Formula IIae with formic acid derivatives.

The reaction of compounds IIae with formic acid esters of the formulaHCOOA leads directly to aldehydes of the formula Z--CHR CHO. However,since the reaction readily goes beyond the aldehyde stage, it isadvantageous to work with an excess of the ester and at a temperature,e.g., l00 to 50 C.

Orthoformic acid esters of the formula HC(OA) react with the compoundsIIae with the formation of acetals of the formula Z-CHR CI-l(OA) Byworking up the reaction mixture in an acidic medium, the free aldehydesof the formula Z--CHR -CHO are obtained. The reaction is mostadvantageously effected with equimolar amounts of reactants. First, thereaction mixture is allowed to react for several hours under coldconditions and then the mixture is heated to 50-80 C., optionally whilereplacing a low-boiling inert solvent, e.g., ether, by a higher-boilingsolvent, e.g., benzene.

Schiff bases of the formula Z-CHR -CH=NAr are obtained by reacting theorganometallic reagents Ilae with N-(alkoxymethylene)-arylamines of theformula AO-CH=NAr, e.g., ethoxymethylene aniline. This reaction takesplace under very gentle conditions and is usually terminated afterboiling the components for one-half hour in an ether solution. Bydecomposing the reaction mixture with ice and hydrochloric acid, thealdehydes (ZCHR CHO) are directly obtained.

Also, substituted formamides, usually formyl monoalkylanilines of theformula CHO-NAAr or formyl diarylamines of the formula CHO-NA1'2, can bereacted with organometallic reagents of the Formula Ilae. Ordinarily,the reaction is conducted at room temperature. The formamides areemployed in excess and the aldehyde ammonias formed as an intermediateare decomposed by working up the reaction mixture in an acidic medium,with the formation of the desired aldehydes. Preferred formamides areN-methylformanilide and N-phenylformanilide.

b. To produce the compounds of Formula I, it is also possible to treatcompounds of the formula Z-X (Ilb) with a dehydrogenating and/oroxidizing agent.

Suitable starting compounds of Formula Ilb are, for example, thosewherein X is CHR CH=CHR CR CHR COR wherein R is H or any desired organicradical, preferably A, Ar, CN or COOH, since the part of the moleculecarrying the R group is removed by oxidation so that the exact nature ofthe R group is not critical, CHR CH -R wherein R is a hydroboron,boroalkyl, or aluminum alkyl group, an alkali metal or an alkaline earthmetal halide group, or CR R wherein R is =CH (OH, CH or the group OCHAccording to the oxidation conditions described in the literature,suitable oxidizing agents are, for example, air or oxygen, preferablywith the addition of a catalyst, e.g., Mn, Co, Fe, Ag or V 0 silveroxide, optionally also together with copper oxide; H O preferably in thepresence of an alkaline agent; organic peracids, e.g., peracetic acid,perbenzoic acid, perphthalic acid; potassium permanganate in an aqueousor acetonic solution and/or an acidic, neutral, or alkaline medium,optionally with the addition of MgSO chromic acid or CrO e.g., in aceticacid or acetone, or in an aqueousacetonic solution in the presence ofsulfuric acid; HNO and the salts thereof; HNO and the salts thereof, forexample 2-68% strength nitric acid, optionally under pressure (up toatmospheres); nitrogen oxides; HClO or the salts thereof, e.g., NaClO;MnO e.g., in dilute sulfuric acid or in a suspension in inert organicsolvents, for example petroleum ether; PbO lead tetraacetate, e.g., inacetic acid or benzene, optionally with the addition of some pyridine;SeO,; N- haloamides, e.g., N-bromo-succinimide, for example in aceticacid/sodium acetate or in pyridine; m-nitrobenzenesulfonic acid; H 10and the salts thereof; ozone;

NaBiO and a mixture of sulfur and an anhydrous primary or secondaryamine, e.g., morpholine.

Examples of suitable solvents for these oxidations are water or aqueousalkali solutions; carboxylic acids, e.g., acetic acid; alcohols, e.g.,methanol, ethanol, isopropanol, or tert.-butanol; ethers, e.g., diethylether, THF, dioxane; ketones, e.g., acetone; hydrocarbons, e.g.,benzene; amides, e.g., DMF or hexamethylphosphoric triamide; andsulfoxides, e.g., DMSO. Also suitable are mixtures of these solvents,especially mixtures of water with an organic solvent. The temperaturesduring the oxidation step range from 30 to 300 C., depending on themethod employed.

Characteristic oxidation methods are, for example: 2-Oxocarboxylic acidsof the formula Z--CH- R --CO-COOH can be decarbonylated by oxidation,for example with aqueous-alkaline H to carboxylic acids of the formulaZ--CHR COOH. A decarbonylation is likewise possible in a sulfuric acidor hydrochloric acid solution in the presence of an oxidation agent. Inan alkaline solution, the reaction is advantageously conducted at atemperature from 0 to 25 C. The 2-oxocarboxylic acids are obtainable,for example, by the reaction of 2-acyldibenzofurans and/ordibenzothiophenes of the formual ZCOR with acetylglycine to thecorresponding azlactone and alkaline hydrolysis.

Unsaturated compounds of the formula Z-CI-I- R CI-I=CHR e.g., wherein RCN, which are obtainable by reacting a carbonyl compound Z- CO- R withacrylonitrile in the presence of triphenylphosphine in cyclohexanol,and/or of the formula ZCHR C CR can be converted, for example. byoxidation into aldehydes of the formula Z CHRg-CHO or into carboxylicacids of the formula ZCI-IR -COOH, depending on the choice of theoxidation agent and the conditions. An oxidation with KMnOi or 0 0leads, first of all, to the 1,2-glycols Z-CI-IR2-CI-IOHCHOHR, which canbe split, for example with H 106, to form the corresponding aldehydes.

An oxidation of the olefinic double bond with ozone, e.g., in CH CI orethyl acetate, leads to ozonides which can be split reductively by meansof zinc in acetic acid, or by catalytic hydrogenation onpalladium/calcium carbonate to aldehydes (I, R CHO). On the other hand,they can be converted, with stronger oxidation agents, into carboxylicacids (1, R COOH).

Compounds of Formula IIc carrying groups with functional groups onadjacent carbon atoms, e.g., 1,2- diols, 1,2-ketols,2-hydroxy-carboxylic acids, or 1,2- hydroxy-amines can be split, forexample, with lead tetraacetate, with NaBiO or with H between the carbonatoms carrying the functional groups, to form an aldehyde function. Thelead tetraacetate oxidation is suitably accomplished with thestoichiometric amount of oxidation agent in an inert solvent, such asacetic acid, chloroform, tetrachloroethane, benzene, or nitrobenzene attemperatures of between 0 and 60 C.

When conducting the oxidation with periodic acid, an aqueous medium issuitably utilized. Advantageous solubilizers for the glycol areemulsifiers, dioxane, acetic acid or tert.butanol. The reactiontemperature ranges suitably from 0 to C.

Compounds of the formula ZCHR CH -R can be converted into thecorresponding compounds of Formula I by oxidation. For this purpose, itis unneces- :sary to isolate the organoboron or organometallic compoundsrequired as the starting materials in the pure form. Instead, they canbe oxidized directly in the reaction mixture in which they wereproduced.

In one mode of operation of this reaction, an ethylene derivative of theformula ZCR =CH is first reacted with diborane. For this purpose, a B li solution or a complex boron hydride, e.g., NaBI-I and a Lewis acid,e.g., BF -etherate, are added, for example, to a solution of the olefinin, e.g., THF or dior triethylene glycol dimethyl ether at a temperaturefrom about -C. to the boiling point of the solvent, and the thusproducedtrisubstituted borane is then oxidized, optionally after decomposing theexcess complex hydride with water. Depending on the oxidation agentemployed and the oxidation conditions, various products of Formula I canbe obtained. For example, by oxidizing with H 0 with the addition of abase, e.g., NaOI-I, preferably at a temperature of from 20 to 60 C.,alcohols (I, R, CI-I OI-I) are produced, whereas oxidation with anexcess of CrO preferably in aqueous acetic acid at about 040 C., andafter a reaction time of about l-48 hours, leads to the carboxylic acids(I, R COOH). Alkylaluminum compounds can be used in place of thediborane, which former compounds can be added and split by oxidation inan analogous manner.

Furthermore, the dibenzofurylor dibenzothienylethyl metal and metalhalide compounds of the formula ZCI-IR CI-I M, obtainable from thehalogenides of the formula ZCI-IR CH l-Ial with alkali metals,preferably Li, or alkaline earth metals, preferably Mg, can be treatedwith an oxidation agent for conversion into compounds of Formula I (Roptionally functionally modified CI-I OH-group). In a preferredembodiment of this method, oxygen is passed through a solution of thecorresponding Grignard compound of the formula Z--CI-IR CH -MgI-Ial inan inert solvent, e.g., ether, THF, or dioxane, at a temperature ofabout 40 to C. After the usual workingup procedure, alcohols of theformula ZCHR CH OI-I are obtained.

In a modification of this variant of the process, a compound of theformula Z--CR =R is treated with sulfur and an anhydrous amine at anelevated temperature, preferably at at least 100 C., until a thioamidehas been formed. The reaction mixture should contain at least 2,preferably at least 3 molar equivalents of sulfur in finely dividedform. At least 2 molar equivalents of amine should be employed. Anyprimary or secondary aliphatic or alicyclic amine can be used in thisreaction, e.g., primary or secondary hydrocarbon amines of up to 12carbon atoms, e.g., methylamine, dimethylamine, ethylamine,diethylamine, n-butylamine, nhexylamine, n-octylamine, etc. Alsosuitable are cyclic amines, which can be substituted by alkyl groups andcan contain oxygen in the ring structure, e.g., piperidine, morpholine,etc. Morpholine is preferred, since this compound makes possibleconducting the reaction at ambient pressure. No solvent is necessary inthe reaction mixture. However, if desired, pyridine or an excess amine,DMF, etc., can be used. The reaction time depends primarily on thereaction temperature; ordinarily, 4-48 hours are sufficient. Thethus-obtained thioamide of the formula ZCHR CSNR wherein the R N groupcorresponds to the starting amine R NH, can optionally be hydrolyzed tothe corresponding carboxylic acid (I; R =COOH). It is not nec- 15 essaryto isolate the thioamide from the reaction mixture.

0. Compounds of Formula I can also be obtained by the reduction ofcompounds of Formula 110.

Typical compounds of the Formula llc are those of Formula llca, Ilcb orIlcc, for example:

' Ilca wherein R is an alkylidene of up to 4 carbon atoms, correspondingto R Ilcb wherein R is =Cl-IR or -OCH and R is an esterified oretherified Ol-I-group;

llcc wherein R is a group removable by hydrogenolysis, especially OH,OAc, Hal, SH, NH aralkyloxy or aralkylamino, each of up to carbon atoms.

The reduction of these starting substances can be suitably effected bycatalytic hydrogenation or by chemical methods.

The starting materials can be treated with hydrogen, for example in thepresence of a catalyst, at pressures of about 1 to about 200 atmospheresand at temperatures of about 80 to 200 C., preferably 20 to 100 C. Thehydrogenation is advantageously accomplished in the presence of an inertsolvent, e.g., water, aqueous sodium hydroxide solution, lower alcohols,e.g., methanol, ethanol, isopropanol, n-butanol, esters, e.g., ethylacetate, ethers, e.g., THF or dioxane or carboxylic acids, e.g., aceticor propionic acid. It is also possible to utilize solvent mixtures. Forthe hydrogenation, the free compounds He can be employed, or also thecorresponding salts, e.g., the hydrochlorides or sodium salts. Suitablecatalysts are, for example, noble metal, nickel and cobalt catalysts.The noble metal catalysts can be provided on supports, e.g., oncharcoal, calcium carbonate, or strontium carbonate, as oxide catalysts,or as finely divided metallic catalysts, e.g., platinum and palladium,which are preferred, and ruthenium or rhodium. Nickel and cobaltcatalysts are suitably employed as Raney metals. Nickel can also be usedon kieselguhr or pumice as the support. Another suitable catalyst iscopper-chromium oxide. With this catalyst, it is simultaneously possibleto effect a reduction of any ester groups present in the molecule toalcohols.

Preferably, normal pressure is utilized during the hydrogenation ofmultiple bonds, and the reaction is carried out so that thehydrogenation is terminated after absorption of the stoichiometricamount of hydrogen. It is basically possible to operate in an acidic,neutral or basic range.

Also suitable as a reducing method for the compounds of Formula llc isthe reaction with nascent hydrogen. The latter can be produced, forexample, by treating metals with acids or bases, e.g., the systemszinc/acid, zinc/alkaline solution, iron/acid and tin/acid.

o H -CH/ (R CHR to aldehydes (I, R, CHO). Also suitable for theproduction of the nascent hydrogen is sodium or another alkali metal ina lower alcohol, e.g., ethanol, isopropanol, n-butanol, amyl alcohol andisoamyl alcohol, or in phenol. An aluminum-nickel alloy in an alkalineaqueous solution, optionally with the addition of methanol, can likewisebe used for this purpose. Sodium or aluminum amalgam in anaqueous-alcoholic or aqueous solution can also be employed for producingthe nascent hydrogen. The reaction can also be effected in aheterogeneous phase, wherein an aqueous phase and a benzene or toluenephase are advantageously utilized. In this reducing method, temperaturesof about 0 to about 150 C., preferably 20 C. to the boiling point of thesolvent employed, are employed.

Other suitable reducing agents are metal hydrides, particularly complexmetal hydrides. This is especially advantageous when it is desired tosimultaneously a reduction of the group R to the aldehyde or alcoholstage. Suitable hydrides of this type are, for example, lithium aluminumhydride, sodium borohydride, e.g., in the presence of aluminum chlorideor lithium bromide, calcium borohydride, magnesium borohydride, sodiumaluminum hydride, lithium and sodium alkoxyaluminum hydrides, e.g.,LiAl(OC H H LiAl- (OC H H, LiAl(0tert.C H H, NaAl(OC H H and sodiumtrialkoxy borohydrides, e.g., sodium trimethoxyborohydride. Additionallysuitable reducing agents are dialkylaluminum hydrides, e.g.,

diisobutylaluminum hydride. These reductions are advantageouslyconducted in the presence of an inert solvent, for example, an ether,e.g., diethyl ether, THF, dioxane, l,2-dimethoxyethane, or diglyme.Sodium borohydride can also be used in an aqueous or aqueous-alcoholicsolution. The reaction takes place preferably at temperatures of from toC., especially from 20 C. to the boiling point of the solvent employed.An inert gas atmosphere, e.g., N, or argon, can be used in thisreaction. The thus-formed metal complexes can also be decomposed in theusual manner, e.g., with moist ether or with an aqueous ammoniumchloride solution. As is known in the art, depending on the conditionsemployed, reduction of unsaturated esters of the type ZC(=R )-COOA withLiAlH, results in various products, for example, in aldehydes (I, R,CHO) or alcohols (I, R, CH OH).

Another preferred reducing agent especially suitable for the removal ofa tertiary OH-group in a starting compound of the formula ZCR,R -OH istin(ll) chloride, which is preferably utilized in the form of thedihydrate thereof in an aqueous, aqueous-alcoholic, or aqueous-acidicsolution, e.g., in the presence of acetic acid and/or hydrochloric acid.This reagent is suitably used at temperatures of between about 0 and C.This reagent is usable as a reducing agent in the preferred method ofsynthesizing the acids and esters of Formula I described below.

A dibenzofuran or dibenzothiophene of the formula ZH is reacted, in aFriedel-Crafts reaction, with ethoxalyl chloride to the corresponding2-(2- dibenzofuryl)- or 2-(2-dibenzothienyl)glyoxylic acid ethyl ester,respectively, which are converted, with an organometallic compound ofthe formula R M, into the corresponding tertiary hydroxy ester of theformula Z-CR (Ol-l)COOC l-I which can be reduced, with tin(ll) chloride,to the desired ester ZCH- R -COC H When operation under hydrolyzingconditions, carboxylic acids of the formula Z-Cl-l- R -COOl-l areobtained.

Another reducing agent is hydriodic acid, optionally with the additionof phosphorus and//or solvents, e.g., acetic acid, preferably at atemperature of from 100 C. to the boiling temperature. 0x0 groups, inparticular, can thus be reduced to CH -groups.

Additional suitable reducing agents are, for example, sodium dithionitein an alkaline or ammoniacal solution; iron(ll) hydroxide; hydrogensulfide and the derivatives thereof, especially metal hydrogen sulfides,metal sulfides and polysulfides; S0 and the derivatives thereof, e.g.,bisulfites and sulfites.

It is also possible to reduce, in compounds of the Formula Ilc, one ormore carbonyl groups to CH -groups in accordance with the methods ofClemmensen or Wolff-Kishner known in the literature.

The Clemmensen reduction can be conducted, for example, by treating thecarbonyl compound with a mixture of zinc and hydrochloric acid,amalgamated zinc and hydrochloric acid, or tin and hydrochloric acid.This reaction is conducted, for example, either in an aqueous-alcoholicsolution or in a heterogeneous phase with a mixture of water and benzeneor toluene. The reaction is preferably effected at a temperature of from20 to 130 C., especially at the boiling temperature of the reactionmixture. The metal can either be supplied first and the acid addedthereto dropwise, or conversely, the acid can be supplied first and themetal can be added in batches.

The Wolff-Kishner reduction is accomplished, for example, by treatmentof the carbonyl compounds with hydrazine in an autoclave and/or in abomb tube at reaction temperatures of from 100 to 250 C. An advantageouscatalyst in this reaction is sodium alcoholate. The reduction can alsobe modified by using hydrazine hydrate as the reducing agent andexecuting the reaction in an alcohol or in a high-boiling water-misciblesolvent, e.g., diethylene glycol or triethylene glycol and/or in thepresence of a strong base, e.g., NaOl-I, KOH, or K-tert.butylate. Thereaction mixture is normally refluxed for about 3-4 hours. Thereafter,the water is distilled off and the residue heated for a period of timeto a temperature of up to about 200 C. During this step, the formedhydrazone is decomposed and the CO-group is converted into a CH -group.

It is also possible to replace Hal-atoms by hydrogen by converting thecorresponding Hal-compounds into the associated organometal, e.g.,Grignard, compounds, and hydrolyzing the latter with water or diluteacids. Y

By the above-described methods, it is possible to reduce severalreducible groups in a given starting compound, wherein the compounds ofFormula IIC are passed through an intermediate stages of the reaction,but need not be isolated. Furthermore, an R and/or R group in thestarting compound can be reduced to another group R and/or R Thus, forexample, one obtains 2-(7-ethyl-2-dibenzofuryl)valeric acid from2-(7-acetyl2-dibenzofuryl)- 4oxopentanoic acid, according toWolff-Kishner or Clemmensen, or 2-( 7-amino-2-dibenzofuryl)-propionicacid from 2-(7-nitro-2-dibenzofuryl)-2-hydroxypropionic acid by reactionwith SnCl d. Compounds of Formula I can also be produced from compoundsof Formula lld by thermolysis or solvolysis'.

Additional functional groups in the X groups which can be removed bythermolysis or solvolysis are, for example, carboxyl groups, which canbe removed by decarboxylation.

Acyl groups, particularly acetyl groups, can be split off by treatmentwith a strong alkali (acid cleavage). It is also possible, for example,to remove the 0x0 group of 2-oxocarboxylic acids in the form of carbonmonoxide or to split off CO from these acids with the formation of thebasic aldehyde and/or aldehyde derivative.

Starting compounds suitable for the decarboxylation are, for example,compounds of the formula ZCR,. R COOH wherein R, preferably is anoptionally functionally modified COOl-I-group. Such malonic acidderivatives can be obtained, for example, by the condensation of a2-dibenzofurylor 2-dibenzothienylacetic acid ester of the formula Z-Cl-lCOOA with an oxalic acid dialkyl ester to the corresponding 2-(2-dibenzofuryl)- or 2-(2-dibenzothienyl)-3-oxosuccinic acid diester. Thedecarbonylation of these compounds results in 2-(2-dibenzofuryl)- or2-dibenzothienyl)- malonic esters which, in the form of their sodiumderivatives, can be alkylated with a compound of the formula R -Hal. Thethus-produced diesters of the formula ZCR (COOA) can subsequently besaponified, optionally partially.

A decarboxylation of these starting substances can, as described in theliterature, be accomplished, for example, by dry heating or by warmingin a solvent, e.g., water, ethanol, dioxane or xylene, to a temperatureof from 50 to 300 C. Suitably, the reaction mixture is heated until theevolution of CO has stopped. It is possible to conduct the reactionunder reduced pressure. CO can also be split off by heating with acids,e.g., a mixture of aqueous hydrochloric acid and acetic acid. Thisreaction can be conducted under an inert gas, e.g., nitrogen.

For acid cleavage, especially suitable are keto esters of the formulaZCR Ac-COOA, wherein Ac preferably is acetyl or benzoyl. These ketoesters can be obtained, for example, by the condensation of esters ofthe formula AcOA, especially alkyl esters of acetic and/or benzoic acid,with esters of the formula Z-CH- --COOA and/or with cyanides of theformula Z-CH CN. The thus-produced keto esters or ketonitriles of theformulae ZCH(COOA)-Ac and Z-CH(CN)Ac, respectively, can thereafter bealkylated as described above, thus obtaining compounds of the formulaeZ-CR (COOA)-Ac and ZCR (C- N)-Ac, respectively. If desired, additionalfunctional modifications can be effected on the ester or nitrile groups.The acid cleavage of the thus produced compounds of the formula Z-CR R-Ac takes place normally by treatment with a strong base, e.g., NaOl-l,KOH, or Ca(OH) in a solvent, e.g., water, lower alcohols, e.g., methanolor ethanol, ethers, e.g., diethyl ether, THF, dioxane, hydrocarbons,e.g., benzene and mixtures thereof. The reaction temperatures range fromabout -l to 200 C. If it is intended to obtain the free carboxylic acidsof Formula I (R, COOI-I), the reaction mixture is preferably heated forseveral hours to a temperature of about 60 to 100 C., optionally underan inert gas, e.g., nitrogen.

It is furthermore possible to produce compounds of Formula I by thedecarbonylation of correspondingly substituted 2-oxocarboxylic acids ofthe formula ZCI-IR -CO-CO()H, which can be obtained by treating glycidicesters of the formula with Lewis acids, e.g., BF followed bysaponification. Thus, it is possible, for example to decarbonylate sucha 2-oxo acid to an acid of the Formula I (R, COOI-I, by heating inconcentrated sulfuric acid.

The 2-oxocarboxylic acids split off CO at temperatures of from 100 to300 C., with the formation of an aldehyde. The decarboxylation isenhanced by the addition of an amine. Colloidal platinum, osmium andruthenium likewise catalyzes the dissociation. Thus, the decarboxylationcan be conducted in the presence of a primary, secondary, or tertiarybase, normally at the boiling point thereof. When a primary amine, e.g.,aniline, is employed, a Schiff base of the aldehyde is produced withsplitting off of H 0 and CO When the reaction mixture is worked up in anacidic fashion, the aldehyde is then liberated. In another embodiment,the bisulfite compounds of the 2-oxocarboxylic acids ZCl-IR --COCOOH canbe decarboxylated at temperatures of about 100 to 300 C., thus obtaininga bisulfite of the corresponding aldehyde.

e. Compounds of Formula I are also produced by the carbonylation ofcompounds of the Formula IIe or-the des-HX, derivatives thereof,optionally in the presence of a reducing agent and/or a catalyst.

Suitable starting compounds for the carbonylation are, for example,compounds of the formulae Z-CH- R Cl, ZCI-IR Br, Z-CI-IR -I, ZCI-IR -OH,as well as ZCR =CH e.g., l-(2-dibenzofuryl)-ethyl chloride, bromide oriodide; l-(2- dibenzofuryl)ethanol; 2-vinyldibenzofuran; l-( 2-dibenzothienyl)-ethyl chloride, bromide or iodide;l-(2-dibenzothienyl)-ethanol; and 2-vinyldibenzothiophene.

The carbonylation can be effected, as described in the literature, bytreatment with gaseous CO, preferably under a pressure of up to 700atmospheres and at a temperature of up to 300+ C., with the addition ofa heavy metal catalyst. It is also possible to contact the startingcompound of Formula Ile to CO in the form of a heavy metal carbonyl. TheCO required for the carbonylation can also be produced directly in situfrom a mixture of formic acid and a mineral acid, preferablyconcentrated sulfuric acid. When operating in the presence of a reducingagent, e.g., gaseous hydrogen, aldehydes of Formula I (R, CHO) areobtained.

Several typical variants of the carbonylation process are the following:

Compounds of the formulae ZCHR -Hal, ZCHR OHor ZCH=R can be reacted witha heavy metal carbonyl, e.g., nickel carbonyl. One embodimentadvantageously uses the halogen derivatives z--CHR -Hal as the startingcompounds, wherein an alkali metal tert.-alcoholate is added as thecatalyst and a lower tert.-alkanol is used as the solvent. At least oneand preferably 3-20 molar equivalents of the heavy metal carbonyl areemployed. Preferred solvents in this reaction are, for example,tert.-butanol, tert.-pentanol, 2-methyl-2pentanol and3-methyl-3-pentanol. Especially suitable alkali metal alcoholates arethe sodium, potassium and lithium derivatives of the aforementionedtert.-alkanols, e.g., sodium, potassium and lithium tert.-butylate. Thereaction mixture should contain at least one and preferably 2-5 molarequivaients of the alkali metal alcoholate. Reaction temperatures canrange from about 0 to about 120 C., preferably between 30 and 100 C.Reaction times of one hour up to about 4 days are required for thereaction. Under these conditions, the tert.-alkyl esters of thecorresponding carboxylic acids of Formula I (R COOI-I) are obtained,which need not be isolated, but instead can be saponified in situ to thefree acids.

In another embodiment, a compound of the Formula IIe, preferably ZCH=Ror Z-Cl-IR OH, is reacted with the heavy metal carbonyl, preferablynickel carbonyl, suitably in an inert solvent, such as THF, dioxane,acetone, in the presence of water. An inorganic acid, e.g., I-ICl, HI-IBr, I-lI, H PO can be present in the reaction mixture. The reactiontemperatures range, for example, from about 20 to about C. The reactioncan be accelerated by irradiation, for example, with a mercury-vaporlamp. Depending on the conditions, the reaction usually requires about 2hours to 2 days to go to completion.

When using formic acid-lsulfuric acid as the cabony lation reagent,suitable starting compounds are the 2- vinyldibenzofurans or-dibenzothiophenes and the carbinols of the formula ZCHR -OI-I. Thestarting compounds are reacted, for example, at temperatures of about040 C., with a mixture of formic acid and a concentrated sulfuric acid,which can contain 050% acetic acid or trifluoroacetic acid. Ordinarily,reaction times of about one minute to 4 hours are required. The reactionmixture should contain at least 2 and preferably 5-20 molar equivalentsof formic acid.

Carbonylation with gaseous CO is advantageously conducted under apressure of IOU-700 atmospheres in an inert solvent, suitably a loweralcohol, e.g., methanol, ethanol, propanol, isopropanol, n-butanol,npentanol, n-hexanol or a cycloalkanol, e.g., cyclohexanol. Examples ofsuitable catalysts are nickel or cobalt carbonyls or halogenides,palladium dichloride, rhodium trichloride (preferably in the form of thetrihydrate), or a compound of the formula [(R P] PdCl wherein R is analkyl, cycloalkyl, aryl or aralkyl group, preferably of up to 10 carbonatoms, e.g., (bis (triphenylphosphine) palladium dichloride. During thisreaction, up to 10% by weight of an organic or inorganic, preferablystrong, acid can be present, e.g., I-ICl, I-IBr, H 80 p-toluenesulfonicacid and methanesulfonic acid.

It is also possible to react compounds of Formula Be, especiallyunsaturated compounds of the type ZCI-I=R and halogenides of the formulaZ-CI-I- R -I-Ial, with a mixture of CO and H in the presence of a heavymetal catalyst, especially a cobalt catalyst, e.g., cobalt (II) acetate,pulverized cobalt, or preferably dicobalt octacarbonyl, to obtainaldehydes of Formula I (R CHO). In this reaction, pressures of about 10to about 250 atmospheres and temperatures of about to 200 C., andoptionally an inert solvent, for example, an ether, e.g., diethyl ether,THF, 1,2- dimethoxyethane and/or a ketone, e.g., acetone, are employed.

f. Haloketones of the formula ZCOCHR I-Ial, obtainable by thehalogenation of ketones of the formula ZCO-CI-hR or from diazoketones ofthe formula ZCOCR N by reaction with hydrogen halide in ether or by aFriedel-Crafts acylation of dibenzofurans or dibezothiophenes of theformula ZI-I, respectively, with haloacyl halides CHR I'Ial--COHal,e.g., Z-chloropropionyl chloride, can be rearranged into acids of theformula ZCI-IR COOI-I in accordance with the Faworskii method describedin the literature, for example, in boiling toluene or xylene in thepresence of a strong base, e.g., NaOH, or by heating in anaqueous-ethanolic silver nitrate solution.

g. Amides of Formula I (R CONI-IR can be obtained by subjecting acarbonyl compound of Formula Ilg (X COR to a Schmidt degradationaccording to methods disclosed in the literature with HN preferably inan inert solvent, e.g., benzene or chloroform, and in the presence of anacidic catalyst, e.g., concentrated sulfuric acid, at a temperature ofabout -40 to +100 C.

Amides of Formula I can also be prrnuced by subjecting an oxime of theFormula IIg (X C(=NOI-I- )R to a Beckmann rearrangement, as described indetail in the literature, with an acidic agent, e.g., concentratedsulfuric acid, polyphosphoric acid, phosphorus pentachloride, orbenzenesulfochloride, preferably at a temperature of from 80 to 180 C.

h. The conversion of epoxides of Formula IIh, especially those offormulae IIha IIhd:

into compounds of Formula I (R, CHO) can be accomplished basicallyaccording to the rearrangement reactions described in the literatureunder catalytic or thermal conditions, thus splitting off CO from thecarboxylic acids IIhc or IIhd, respectively. For catalyticallycontrolled rearrangements, the epoxide is caused to react with thecatalyst in a suitable solvent. Suitable solvents for the rearrangementreactions are inert solvents, e.g., benzene, toluene, xylene, CClacetonitrile, ether, THF, dioxane, alcohols, e.g., ethanol, propanol,butanol or acids, e.g., formic acid, acetic acid, both as anhydroussolvents and in mixture with water. The rearrangement can also beeffected on the interphase of two solvents immiscible with each other,wherein one phase contains the catalyst and the other the compound to berearranged. Preferred catalysts are mineral acids, e.g., H 80 HCl, HBr,HF, HCl0 organic acids, e.g., formic acid, acetic acid, oxalic acid,p-toluenesulfonic acid; Lewis acids, e.g., BF AlCl ZnCI MgBr FeCl andSnCl The rearrangement can be accomplished, for example, by heating asolution of the epoxide in THF with 25% strength sulfuric acid or withBF p-toluenesulfonic acid, or ZnCl as the catalyst in anhydrous benzene.The rearrangement can also be conducted with the aid of agents whichsplit off water, e.g., polyphosphoric acid, which can simultaneouslyserve as the reaction solvent.

The epoxides can also be thermally rearranged, for example, bydistillation or by heating in a sealed apparatus. In this connection,the glass surface of the apparatus can function as the catalyst. Therearrangement can also be accelerated by adding small amounts of acatalyst, e.g., ZnCl For the rearrangement of the epoxides, it is alsopossible to employ solid catalysts, e.g., copper, copper bromide,magnesium silicates, aluminum oxides and chromium oxide tungsten oxidecontact catalysts. In these reactions, temperatures of from to 300 C.and pressures between reduced pressure and 200 atmospheres are employed.The carboxylic acids IIhc and IIhd, respectively, are suitably splitthermally under reduced pressure with the addition of copper or copperbromide as catalyst. The rearrangement can be conducted in the gaseousor liquid phase, depending on the stability of the epoxide and the typeof catalyst. A brief heating of the epoxides with concentrated NaI-ISOsolution yields directly the corresponding sodium bisulfite additioncompounds of Formula I (R CHOI-ISO Na).

The epoxides of Formula IIha or Ilhb can be obtained for example, byreacting ketones of the formula Z- COR with alkyl-magne sium halides,hydrolysis to the carbinols, dehydration to ethylene derivatives of theformula ZCR CHR and epoxidation with peracids, e.g., perbenzoic acids.The epoxides can also be produced from the chlorohydrins of the formulaZ CR (OH)CHR --Cl by treatment with a base, thus splitting off I-ICl.These chlorohydrins can be obtained, in turn, from chloroketones of theformula Z- CO--CH --Cl by reaction with methylor ethylmagnesium iodide,or by reduction. It is also possible to react chloromethyl ketones ofthe formula R COCI-I Cl with organometallic compounds ZM, with theepoxide not normally being isolated. Thus, 2-(2- ZCII--CR -COOH IIhddibenzofuryl)-butanal is produced from Z-dibenzofurylmagnesium bromideby reaction with chloromethyl ethyl ketone. In other cases, theisolation of the epoxides IIh often is unnecessary. Thus, for example,the corresponding epoxide can be prepared from 2-chloro-2-(2-dibenzofuryl)-propanol by treatment with a base, and thisepoxide is rearranged in situ without isolation into2-(2-dibenzofuryl)-propanal by treatment with an acid.

The epoxy acids IIhc and IIhd are advantageously obtained bycondensation of ketones of the formula Z- CO-R with ethyl chloroformateand subsequent alkaline saponification. It is advantageous not toisolate these epoxy acids but instead the alkaline saponificationmixture is adidified and heated until termination of thedecarboxylation, thus obtaining the desired aldehydes (I, R, CHO). Theepoxy acids, and/or the esters thereof, can also be prepared byexpoxidation of the acrylic acids Z--CR =CI-I-COOI-I and/or the estersthereof.

i. Aldehydes of Formula I (R, CI-IO) can be produced by splitting off HXfrom compounds of the Formula IIi, especially by dehydrating glycols ofthe formula ZCR (OH)-CI-IR OI-I, preferably ZCR- (Ol-I)-CH OH, but alsoZCHOI-I-CHR,--OH, which process takes place by a rearrangement which iscatalyzed by acids, metal halides, Lewis acids or solid catalysts.Advantageous acids are I-ICl, I-IBr, H 50 H PO H S0 I-IClO HCOOI-I, CHCOOl-I, oxalic water from the molecule can be effected with or withoutan inert solvent. It is also feasible to employ an excess of the acid asthe solvent, e.g., formic acid, acetic acid, trifluoroacetic acid,sulfuric acid, or polyphosphoric acid. Additional suitable solvents are,e.g., hydrocarbons, e.g., toluene, benzene, xylene,tetrahydronaphthalene, decahydronaphthalene; halogenated hydrocarbons,e.g., chlorobenzene; ethers, e.g., anisole, THF, dioxane, diethyl ether,diisopropyl ether, 1,2- dimethoxyethane, diethylene glycol dimethylether; alcohols, e.g., ethanol, propanol, butanol; also DMF,dimethylsulfone, DMSO, hexamethylphosphoric triamide; N-ethylmorpholine,water and mixtures thereof. The reaction can be accomplished inanhydrous solvents or in the presence of water. In some cases, theaddition of water is advantageous in order to dissolve the catalyst.When anhydrous conditions are employed, the water produced during thereaction can be bound by suitable additives, e.g., molecular sieves(such as surface-active aluminum silicates), or it can be removed, forexample, by a water trap when using toluene as the solvent. Preferably,the reaction is carried out in a temperature range of from 10 to 200 C.,especially advantageously at the boiling point of the selected solvent.In addition to the desired aldehyde, the rearrangement can also yieldthe corresponding isomeric ketone as a by-product. No difficulties areencountered in the separation of the aldehyde, which can be effected,for example, via the bisulfite compound.

In addition to the glycols of Formula IIi (X OH, R H), the monoesters ormonoethers of the Formula Ili (X, OH, R Ac and A, respectively) thereofcan likewise be converted into the corresponding aldehydes (I, R, CHO)by an acid-catalyzed rearrangement. The monoethers can readily beobtained from the ketones of the formula Z-COR by Grignard synthesiswith chloromethyl alkyl ethers of the formula ClCI-I O--A. Thus, forexample, 2-(2-dibenzofuryl)- propanal is produced fromZ-methoxy-l-methyl-l-(Z- dibenzofuryl)-ethanol by refluxing with formicacid or anhydrous oxalic acid. The conversion of the esters or ethersIIi (X, OH, R,, Ac and A, respectively) into the aldehydes I (R, CHO)can basically be conducted in accordance with the methods described forthe diols [H (X, OH, R H).

Enol ethers of the formula ZCR =CHOA can be produced by splitting offwater from the compounds of the formula Z--CR (OH)-CH OA. Thedehydration is accomplished, for example, with P in pyridine, withpolyphosphoric acid, molecular sieves, dehydrating oxides, or byazeotropic dehydration.

Also, compounds of the general Formula IIi (X, Hal) can be convertedinto compounds of the general Formula I by dehydrohalogenation. Suitablereagents splitting off hydrogen halide or organic or inorganic bases,which are generally employed for this purpose, e.g., triethylamine,tributylamine, pyridine, lutidine, quinoline, N-methylpiperidine,tert.-butylamine, collidine, 1,5-diazabicyclo[3,4,0]nonene-(5),'dimethylan- 24 iline, tetraethylammonium chloride, 1 ,4-diazabicyclo[2,2,2]octane, DMF, potassium tert.-

butylate in DMSO, NaHCQ Li CO LiBr, LiCl, MgBr NaI, KOI-I, NaOH, NaNI-IAg O, CH COONa, C H Na and A1 0 A suitable solvent is either an excessof the selected base, if liquid, or a solvent described in theliterature for dehydrohalogenation reactions, e.g., DMSO, acetone;ether, e.g., diethyl ether, THF, dioxane; acetonitrile; alcohols, e.g.,methanol, ethanol or tert.-butanol; water; or mixtures of theabove-mentioned solvents. Thus, for example, 2-(2-dibenzofuryl)-propanal is obtained from 2-(2-dibenzofuryl)-2-chloro-l-propanol by treatment with pyridine or1,5-diazabicyclo[3,4,0]nonene-(5) under heating, or from2-(2-dibenzofuryl)-2-bromo-lpropanol by treatment with dimethylaniline.As byproducts, the corresponding epoxides are partially obtained, whichcan be converted into the aldehydes by treatment with an acid, asdescribed above.

j. Compounds of Formula I can also be obtained by reacting ketones ofFormula II] with triphenylphosphine alkoxymethylenes of the formula ArP=CH- 0A, which can be produced, normally in situ, from atriphenylphosphine and alkylor aryl-halogen methyl ethers by theaddition of a base thereto. In this reaction, the product is notisolated. Instead, the reaction mixture is directly reacted with theketones IIj. Inert anhydrous solvents are suitably employed, e.g.,ether, THF, dioxane, benzene. Strong bases, such as organometals andalkali metal alkoxides, e.g., C H Li, n-C.,H Li, K-tert.-butylate, NaOCH are advantageously used for liberating the triphenylphosphine alkoxyoraryloxymethylenes. The reaction is conducted at temperatures of betweenabout and l00 C. Thus, for example, l-methoxy-2-(2-dibenzofuryl)-propeneis produced from Z-acetyI-dibenzofuran by reaction withtriphenylphosphine methoxymethylene.

k. Compounds of Formula I (R, optionally functionally modified CHOH-group) can also be obtained by subjecting a halogen compound of theformula Z-CHR CH I-Ial (Ilk, X Hal) to hydrolysis, alcoholysis oracidolysis, or by reaction with a metallic salt and/or metallicalcoholate of the formula R OM,.

Thus, for example, alcohols of Formula I (R, CH OH) are produced bysaponifying a halogen compound of the formula ZCHR CH I-Ial in anaqueous or aqueous-alcoholic solution or suspension, optionally with theaddition of a solubilizer, e.g., an alcohol,, glycol or polyglycolether. Preferred saponifying agents are alkalis, e.g., NaOH and KOH, butslurries of Ca(OH) Pb(OH) and AgOH can also be employed. Thesaponification is normally effected at an elevated temperature, e.g., atthe boiling temperature of the solvent. The halogenide IIk can, however,also be reacted in a non-aqueous medium, by agitating the solutionthereof in an inert solvent, e.g., acetone, ether, THF, acetonitrile, orbenzene, with suspended AgOH or Pb(OH) under boiling.

Ethers of Formula I (R, etherified CH OH-group) are obtained by reactinga compound of the formula ZCHR Cl-I Hal with an alkali metal alcoholateor phenolate. Advantageously, the sodium alcoholate is produced bydissolving the required amount of sodium in the respective alcohol,using an excess thereof as the solvent. When using the less reactivechlorides or bromides of Formula IIk (X C1 or Br), a small amount of Klcan be added thereto. The reaction mixture is then suitable refluxeduntil it has become neutral. Aryl ethers are obtained, for example, bymixing an alcoholic alkali metal alcoholate solution with an equivalentof the respective phenol, and further processing the mixture asdescribed for the alkyl ethers. In the production of the aryl ethers,water or aqueous alcohols are additionally suitable as the solvents. Thealkali metal alcoholates or phenolates can also be reacted in asuspension with halogen compounds of the formula Z-CHR CH --Hal, inwhich case an inert solvent is employed, e.g., ether, THF, acetone orbenzene.

Esters of Formula I (R, esterified CH OH-group) are obtained in ananalogous manner by refluxing a compound of Formula lIk in an aqueous,aqueousalcoholic, or alcoholic solution with an alkali metal salt of thecarboxylic acid or sulfonic acid to be esterified. The addition oftriethylamine accelerates the reaction. A preferred method for obtainingacetates of the formula Z--CHR --CH OCOCH resides in refluxing ahalogenide of the formula Z-CHR CH lE-Ial with anhydrous sodium acetatein acetic acid. For the preparation of esters of Formula I (R,esterified CH OH- group), it is also possible to reflux a halogencompound of the formula Z-CHR CH I-lal in an inert solvent, e.g., ether,acetone, chloroform, THF or benzene, with a suspension of the silversalt or lead salt of the acid to be esterified. Diazonium compounds ofFormula IIk (X a diazonium group) are produced when treating amines ofthe formula Z-CHR CH NH with nitrous acid or the derivatives thereof,such as, for example, alkyl nitrites and NOCl. They are split in thepresence of water in accordance with methods known in the literature, toalcohols of the Formula I (R, CH OH). In this case, the reaction isconducted especially advantageously by combining an aqueous solution ofNaNO with a mineral acid or acetic acid solution of the amine at atemperature of -l00 C., and terminating the reaction by heating. Theamines are reacted with alkyl nitrites preferably in an inert solvent,e.g., ether, benzene, THF, an absolute alcohol, e.g., methanol orethanol, or in a water-alcohol mixtures. When using alcohols, ethers, ofthe Formula I (R, etherified OH- group) can also be produced. Whenconducting the reaction in the presence of an acid, e.g., acetic acid,the reaction product is also an ester of Formula I (R, esterifiedOH-group).

1. In accordance with the methods of the Willgerodt reaction describedin the literature, ketones of Formula II] can be converted into amidesof the formula ZCI-I- -CONH with ammonium polysulfides, which can alsobe formed in situ in an aqueous solution from ammonia and hydrogensulfide and/or sulfur. During the reaction of the ketones III with aprimary or secondary amine (preferably morpholine) in the presence ofsulfur, the corresponding substituted thioamides (preferablythiomorpholides) are produced. Suitably, an excess, e.g., up to 1 mole,of sulfur and amines is utilized. In these reactions, an inert solventcan be added, e.g., dioxane or THF. The preferred reaction temperaturesrange from 100 to 200 C., especially from 120 to 160 C. When usingvolatile solvents, the reaction is advantageously carried out underpressure.

The compounds of Formula I can also be obtained by splitting E E from acompound (III) wherein one of the two E groups is a phenolic hydroxy ora mercapto group or a metallic salt derived therefrom (A phenolate orthiophenolate), preferably in the form of a sodium salt. The other ofthe two E groups can be identical to the first or can be, e.g., ahalogen atom, preferably C1 or Br, an amino group or a functionalized,e.g., etheritied or esterified, OH or SH-group. The El-Eg compound to besplit off accordingly depends on the nature of the E group and can be,for example, water, ammonia, hydrogen halide, e.g., HCl or HBr orhydrogen sulfide. The various reagents employed as the media forsplitting off E E will depend on the nature of the starting compound, aswill be apparent to those skilled in the art. For example, if water isto be split off, duitable dehydration agents are, e.g., ZnCl P 0 andpolyphosphoric acid.

Hydrogen halide is suitably split off employing a base, e.g., NaOH, KOH,or Ca(OH) optionally in the presence of a catalyst, e.g., a heavy metal,e.g., copper, preferably in pulverized form. The splitting-off step canbe accomplished in the presence of an additional inert, preferablyhigh-boiling solvent, e.g., in the presence of xylene or Tetralin(tetrahydronaphthalene). However, the reaction is preferably conductedin the absence of a solvent. The reaction temperatures range from about0 to about 250 C. preferably from to 220 C.

It is also possible to proceed in such a manner that the startingmaterial (III) is not isolated but rather is formed in situ in thereaction mixture. Thus, a compound can be the starting substance, forexample, which otherwise corresponds to Formula III, but wherein bothgroups B represent amino groups which are thereafter diazotized anddecomposed by boiling. As the intermediate product, which is notisolated, a diphenyl is produced (III, both groups E OH), which isdehydrated by heating in an acidic solution. It is also possible, forexample, to heat pyrocatechol together with a p-hydroxyphenyl-fatty acidor a p-mercaptophenyl-fatty acid, wherein, as the intermediate product,the aforementioned diphenol or the corresponding2-hydroxy-2'-mercaptodiphenyl derivative, or a compound V (one of thegroups G OH; see below) is most likely formed.

The dibenzothiophenes (I, Y S) are also obtained by treatingcorresponding diphenyl derivatives (IV) with sulfur in the presence of acatalyst. Especially suitable catalysts are Lewis acid, e.g., N01,. Thereaction takes place suitably at higher temperatures, especially from to250 C.

Compounds of Formula I are also obtained by heating a hydroxy ordiazonium compound (V), thus closing the five-membered ring withliberation of nitrogen. Advantageously, the acidic, e.g., hydrochloricor sulfuric, solution in which the diazonium salt is produced is heatedto a temperature of from 80 to C. A hydroxy compound (V, wherein onegroup G OH) can also be produced as an intermediate product in thereaction of 4-R -pyrocatechol with a p-HY-phenyl-fatty acid, e.g., inthe reaction of pyrocatechol with 2-(p-hydroxyphenyl)-propionic acid.

Optionally, one or both of the R, and R groups in a thus-obtainedproduct of Formula I, can be converted into other R, and R groups.

For example, an R group can be converted into another R; group bytreating the product with a solvolyzing, thermolyzing, esterifying,interesterifying, amidating, dehydrating, acetalizing, acylating,etherifying, reducing, oxidizing, or salt-forming agent.

Functional derivatives of the carboxylic acids of the Formula I (R COOH)and functional derivatives of the alcohols of the Formula I (R =CI IOI-I), especially the esters of these compounds (R esterified COOH- orCH OH- group, especially R COOA or CH OAc), can be solvolyzed,particularly hydrolyzed or thermolyzed, to the free carboxylic acids orthe free alcohols, respectively, according to methods described in theliterature. Hydrolysis can be conducted in an acidic or alkaline mediumat temperatures of about 20 to about 200 C., preferably about roomtemperature to the boiling temperature of the selected solvent. Examplesof suitable acidic catalysts are hydrochloric, sulfuric, phosphoric orhydrobromic acid. Suitable basic catalysts are, for example, sodium,potassium and calcium hydroxide and sodium and potassium carbonate.Water is preferably the solvent. Other advantageous solvents are loweralcohols; ethers, e.g., Tl-IF, dioxane; amides, e.g., DMF; sulfones,e.g., tetramethylenesulfone; and mixtures thereof, especially mixturescontaining water. For saponification purposes, the esters are treatedpreferably for about 1-48 hours with K CO in methanol, ethanol orisopropanol at temperatures of about 20 to 80 C. If the saponificationis effected in an acidic medium, acetic acid can also be used as thesolvent. The acid or alcohol derivatives can also be converted intocarboxylic acids or alcohols of Formula I (R COOH or CI-I OI-I), forexample, in ether or benzene with the addition of a strong base, e.g.,potassium carbonate, or in the absence of solvent by melting togetherwith an alkali, e.g., KOH and/or NaOH or alkaline earths, or by heatingwith water under pressure to temperatures of l50-200 C.

A further embodiment of this invention resides in the saponification ofamides of Formula I (R, CONH CONI-IA or CON(A) and thioamides of FormulaI (R, CSN(A) The thioamides or amides are preferably hydrolyzed byheating with an aqueous mineral acid, e.g., hydrochloric acid or with analcoholic alkali. A partial hydrolysis of the thioamides, for example byheating with a mixture of a lower alcohol and water, results in theproduction of the corresponding amide. For the synthesis of2-dibenzofurylacetic acids, it is preferred to hydrolyze thethiomorpholides, which can be obtained by the Willgerodt-Kindler method.

By dry heating of especially tertiary alkyl esters of Formula I (R,COO-tert.-alkyl) to temperatures of between about 50 and 350 C., acidsof Formula I (R, COOH) are produced. The thermolysis can also beconducted in an inert solvent, e.g., benzene, water, DMF, ethyleneglycol, glycerin, DMSO, cyclohexanol, preferably with the addition of acatalytic amount of an acid, e.g., p-toluenesulfonic acid.

Another embodiment of the invention is the hydrolysis of nitriles ofFormula I (R, CN), which can be effected in an acidic medium, e.g., HClor H 80 in water, a lower alcohol, aqueous dioxane or acetic acid, or inan alkaline medium, e.g., KOI-I in an aqueous lower alcohol or incyclohexanol. Partial hydrolysis of the nitriles, for example treatingsame with concentrated sulfuric acid at room temperature or with H in analkaline solution, results in the production of an amide of Formula I (RCONH In a compound of Formula I wherein R, is a functionally modifiedaldehyde group, the aldehyde group can be liberated by treatment with asolvolyzing agent.

Thus, the free aldehydes can be obtained from hemiacetals or acetals bymeans of hydrolysis. The hemiacetals, e.g., those of the formula Z-CHRCHOH-OA, and acetals, e.g., those of the formula Z-CHR -CI-I- (OA) arenormally hydrolyzed very easily with water in the presence of an acid.For the cleavage step, dilute or concentrated mineral acid generally isused, e.g., sulfuric acid, hydrochloric acid, phosphoric acid, or anorganic acid, e.g., oxalic acid, tartaric acid, citric acid. Thecleavage can be accomplished at temperatures of about 20 to +100 C.,preferably +20 to C., in the absence or presence of an additionalsolvent. Thus, the acetals can be dissolved by adding acetone, ethanol,THF or acetic acid, before they are split. The acetals can also bereacted with acids in the presence of anhydrides. Suitable acidanhydrides, which are employed preferably in an equivalent molar ratio,are, for example, acetic anhydride, benzoic acid anhydride, and phthalicacid anhydride. It is also possible to utilize acetyl bromide. Thehydrolysis of the acetals with an aqueous NaHSO solution results, by wayof the aldehydes, in the bisulfite addition compounds thereof, Z-CI-IRCI-IOH-SO Na.

Aldehydes of Formula I (R CHO) can also be produced by splitting ahemi-thioacetal thereof, e.g., those of the formula Z-CI-IR CI-IOASA, orthioacetal thereof, i.e., mercaptals, e.g., those of the formula Z-CHR--CI-I(SA) The hemi-thioacetals are cleaved, for example, with Raneynickel, and the mercaptals are split with HgCl in acetone, TI-IF ordioxane. It is also possible to employ mixtures of I-IgCl and CdCO; orHgCl and HgO for splitting purposes.

Schiff bases, e.g., those of the formula Z-CH- R --CH=NAr can be splitby brief heating with dilute acids, e.g., the above-mentioned mineralacids or oxalic acid, optionally with the addition of a solvent, e.g.,ethanol or acetic acid. The Schiff bases can also be split with Nal-ISOand the thus-formed amine (ArNl-l removed by distillation or extractionand the aldehyde isolated as the bisulfite addition compound orliberated from the latter as described below. The aldehydes can also beliberated by hydrolysis, e.g., by treatment with an acid, of thecondensation products thereof with compounds of the acid amide type, e.g., carboxylic acid amides, sulfonic acid amides, urethanes, ureaderivatives.

Aldehydes of Formula I (R; CHO) can also be obtained by the hydrolysisof hydrazones of the formula ZCHR CH=N-NHR' or azines of the formula(ZCI-IR CH=N) In general, the splitting of these derivatives ispreferably accomplished by acid hydrolysis. For decomposition purposes,a dilute solution of oxalic acid or phthalic acid can be employed. It isalso possible to employ sulfurous acid with heating for split ting theoximes. Also suitable for the splitting reaction are aqueous mineralacids. In this procedure, the compounds to be cleaved are dissolved bythe addition of ethanol, THF, acetic acid, or dioxane. Hydrazones canalso be split by treating them with other carbonyl compounds, e.g.,p-nitrobenzaldehyde, 2,4- dinitrobenzaldehyde, or pyruvic acid. In thethusproduced equilibrium mixture, the aldehyde is liberated, while thecorresponding derivative of the added carbonyl compound is formed, whichis normally of lower solubility. The process is suitably conducted sothat the hydrazone and the carbonyl compound are heated under reflux inan aqueous suspension or in an alcoholic-aqueous solution. If thealdehydes are present in the form of their Girard derivatives T or P,they can be liberated by cleavage with hydrochloric acid or sulfuricacid at temperatures of C. to the boiling temperature of the solventemployed, e.g., water, optionally in mixture with methanol or ethanol.The thusformed aldehyde is extracted from the aqueous phase with asuitable organic solvent, e.g., CI-ICl Oximes of the formula ZCI-IR-CH=NOl-I can also be split by oxidation, which is done by treatmentwith nitrous acid and/or amyl nitrite or FeCl in the presence of anacid.

Bisulfite addition compounds of the formula ZCI-I- R CHOI-ISO M can besplit by treatment with a base or acid, thus liberating thecorresponding aldehyde. The cleavage reaction can take place merely byheating an aqueous solution thereof. More advantageously, the reactionmixture is heated in the presence of dilute aqueous acid, e.g, HCl or H80 of a bicarbonate, e.g., NaHCO of a carbonate, e.g., Na Co or of analkali, e.g., NaOI-I. The splitting step can also be achieved by addinganother carbonyl compound having a greater affinity to bisulfite, e.g.,formaldehyde.

Aldehydes of Formula I (R CI-IO) can also be obtained by splitting enolethers of the formula chloroform or 1,2-dichloroethane, is addedthereto. The esterification takes place under gentle conditions if thewater of reaction is bound chemically by the addition of a carbodiimide,e.g., N,N-dicyclohexylcarbodiimide. In this reaction, an inert solventis used, e.g., ether, dioxane, 1,2-dimethoxyethane, benzene, CH Cl orCI-ICI A base, e.g., pyridine, can also be added. The methyl, ethyl orbenzyl esters can also be produced by reacting the free acids withdiazomethane, diazoethane or phenyldiazomethane, respectively, in aninert solvent, e.g., ether, benzene or methanol. Esters of Formula I (R,esterified COOI-I--group) can also be obtained by the chemical additionof the carboxylic acids (I, R, COOH) to an olefin, e.g., isobutylene,cyclohexene, or to an acetylene, preferably in the presence of acatalyst, e.g., ZnCl BF H 80 arylsulfonic acids, pyrophosphoric acid,boric acid, oxalic acid, at temperatures of about 0 to about 200 C.,pressures of l to 300 atmospheres, and in an inert solvent, e.g., ether,TI-IF, dioxane, benzene, toluene and xylene.

Esters of Formula I (R esterified COOI-I-group) can also be produced byreacting metallic salts of the carboxylic acids of Formula I (R COOH),preferably the alkali metal, lead or silver salts, with an alkylhalogenide, e.g., those of the formula R Cl or R CI, option- ZCR =CI-IOAor ZCR =CI-IOAr. These enol ethers canally in an inert solvent, e.g.,ether, benzene, DMF or be cleaved, for example, with diulte mineralacids, e.g.,

The splitting step can also be effected with acetic acid or NaHCO In thecase of sensitive enol ethers, heating in water to 100 C. underevaporated pressure is sufficient. The cleavage can also be accomplishedwith hydroxylamine hydrochloride or semi-carbazide hydrochloride, inwhich case the aldehydes are isolated in the form of the oximes orsemi-carbazones.

Ethers of Formula I (R CH OA or CH OAr) can be converted into alcoholsof Formula I (R Cl-l OH) in accordance with the ether splitting methodsknown in the literature. For example, the ethers can be split bytreatment with hydrogen bromide or hydrogen iodide in an aqueous oracetic solution, by heating with a Lewis acid, e.g., AlCl or borontrihalide, or by melting with a pyridine hydrohalide or anilinehydrohalide at about 200 C.

From other compounds of Formula I, esters of Formula I (R, esterifiedCOOH or CH OI-Igroup) can be prepared according to methods disclosed inthe literature. Thus, it is possible, for example, to react an acid ofFormula I (R, COOH) with the respective alcohol, or an alcohol ofFormula I (R; CH OH) with the respective acid, especially a carboxylicacid, in the presence of an inorganic or organic acid, e.g., HCl, HBr,l-II, H 80 H PO trifluoroacetic acid,-a sulfonic acid, e.g.,benzenesulfonic acid or p-toluenesulfonic acid, or an acidic ionexchanger, optionally in the presence of an inert solvent, e.g.,benzene, toluene or xylene, at temperatures of about 0 C. to preferablythe boiling temperature of the reaction mixture. Either the alcohol orthe carboxylic acid is preferably employed in excess. Preferred alcoholsare those of the formulae R Ol-I and R OI-I wherein R and R have thevalues given above except H. It is also possible to conduct the reactionin the presence of a water-binding agent, e.g., an anhydrous heavy metalsulfate or molecular sieve. It is also possible to remove the water ofreaction azeotropically, wherein advantageously a hydrocarbon, e.g.,benzene or toluene, or chlorinate hydrocarbon, e.g.,

petroleum ether, or with an alkyl chlorosulfite, e.g., those of theformula A-OSOCI, and subsequent thermolysis of the thus-obtainedadducts.

It is likewise possible to convert acid halogenides, anhydrides andnitriles of Formula I (R; COCl, COBr, COOAc, COOCOCHR -Z and CN) intoesters of Formula I (R, esterified COOH) by reaction with an alcohol,e.g., an alcohol of the formula R OH or R OI-I, if desired in thepresence of an acidic catalyst or a base, e.g., NaOI-I, KOH, Na CO K COor pyridine. Preferably, an excess of the respective alcohol is utilizedand the reaction is conducted at temperatures of about 0 C. to theboiling temperature of the mixture. tert.-Alkyl esters are obtainable,for example, from the corresponding acid chlorides and potassiumtert.-alcoholates in the presence of an inert solvent. Alcohols ofFormula I (R CH OH) and the alkali metal alcoholates thereof can bereacted with the halogenides or anhydrides of the acids to beesterified, without or with the addition of an acid-neutralizing agent,e.g., sodium hydroxide or potassium hydroxide, sodium carbonate orpotassium carbonate or pyridine. Suitable solvents are inert organicsolvents, e.g., ether, TI-IF or benzene. It is also possible to employan excess of the halogenide or anhydride as a solvent. In a preferredmode of operation, the selected alcohol of Formula I (R, CH )H) in apyridine solution is combined with the halogenide and/or anhydride ofthe acid to be esterified.

It is also possible to esterify alcohols of Formula I (R, CI-I OI-I)with ketenes. This reaction is preferably conducted in an inert solvent,e.g., ether, benzene or toluene, and in the presence of an acidiccatalyst, e.g., sulfuric acid or p-toluenesulfonic acid. Thus, 2-( 2-dibenzofuryl)-propyl acetate can be produced, for example, from2-(2-dibenzofuryl)-propanol and ketene.

Esters of Formula I (R, esterified COOI-I-group) can also be prepared bythe transesterification of another ester of Formula I (R COOR wherein Rany desired organic residue, preferably A) with an ex cess of therespective alcohol, or by reacting a carboxylic acid of Formula I (R,COOI-I) with any desired other ester of the selected alcohol, which ispreferably employed in an excess. Analogously, the esters of Formula I(R, esterififed CH OI-I-group) can be obtained by thetransesterification of alcohols of Formula I (R, CI-I OI-I) with anexcess of a lower alkyl ester, e.g., of the formula AcOA, or by thetransesterification of other esters of Formula I (R, esterified CI-lOI-I- group, preferably esterified with a lower carboxylic acid) with anexcess of the carboxylic acid to be esterified. The reaction isconducted in accordance with the transesterification methods describedin the literature, especially in the presence of a basic or acidiccatalyst, e.g., sodium ethylate or sulfuric acid, at temperatures ofabout C. to the boiling temperature. Preferably, the reaction is carriedout so that after the equilibrium has been established, one reactant iswithdrawn from the equilibrium mixture by distillation. Thus, 2-(2-dibenzofuryl)-propanol can be converted into 2-(2- dibenzofuryl)-propylbutyrate with the methyl ester of butyric acid by distilling off themethanol.

Among the esters of Formula I (R, esterified COOH), of particularinterest are those which are readily cleavable under physiologicalconditions, for example the vinyl, tert.-butyl, tetrahydro-2-furyl, andtetrahydro-Z-pyranyl esters, obtainable for example by reacting the freecarboxylic acids with acetylene, isobutylene, 2,3-dihydrofuran and2,3-dihydropyran, preferably in the presence of a catalyst, e.g., ZnClBF H SO,, aryl-sulfonic acids, pyrophosphoric acid, boric acid andoxalic acid, at about 0-l C. in an inert solvent, e.g., ether, TI-IF,dioxane, benzene and xylene.

Esters of Formula I (R, esterified COOH) can also be obtained bysolvolyzing compounds of Formula I wherein R, is a thio ester, iminoether, oximino ether, hydrazone ether, thioamide, amidine, amidoxime oramide hydrazone group, with water or dilute aqueous base or acid, e.g.,ammonia, NaOI-I, KOH, Na CO K CO HCl, H 80 with the addition of therespective alcohol and splitting off, respectively, of hydrogen sulfide,ammonia, amines, hydrazine derivatives and hydroxylamine. Although mostof the imino ether hydrochlorides are usually immediately split into theesters and ammonium chloride in an aqueous solution at room temperature,the solvolysis of other derivatives, e.g., the amidoximes or thioamides,takes place only at higher temperatures, e.g., up to 100 C.

Acids of Formula I (R, COOI-I) can be converted into the correspondingacid halogenides of Formula I (R, e.g., COCl or COBr) in the presence orabsence of an inert solvent by treatment with an inorganic acidhalogenide, e.g., SOCl or SOBr Hydrochlorides of the imino ethers ofFormula I (R, C(=NI-I)OA) can be obtained from the nitriles of Formula I(R, CN) with an alcohol of the formula A-OI-I in ether, in the presenceof I-ICl.

It is also possible to convert the acids of Formula I (R, COOH) and/orthe functional derivatives thereof, preferably the halogenides andesters thereof of Formula I (R, COCl, COBr, and/or esterifiedCOOH-group) into the corresponding amides (or hydroxamic acids) bytreatment with an amidating agent, e.g., ammonia or an amine of theformulae ANH or (A) NH, respectively, or with hydroxylamine. Examples ofsuitable amines are monoalkylamines, e.g., methylamine, ethylamine,n-propylamine, isopropylamine, n-butylamine, isobutylamine;dialkylamines, e.g.,

32 dimethylamine, methylethylamine, diethylamine, di-npropylamine,diisopropylamine, di-n-butylamine,

diisobutylamine; and also aryland aralkylamines, e.g., aniline,benzylamine; hydroxyalkylamines, e.g., ethanolamine, diethanolamine;cyclic amines, e.g., pyrroli' dine, piperidine, morpholine,thiomorpholine, piperazine; N-alkyl-piperazines, e.g., N-methylorN-ethylpiperazine; N-hydroxyalkylpiperazines, e.g.,N-2-hydroxyethylpiperazine. It is possible, but not required to add aninert solvent during the production of the amides, e.g., an alcohol,e.g., methanol or ethanol or a chlorinated hydrocarbon, e.g., CHCl It islikewise possible, but not required, to employ pressure, e.g., up toabout 200 atmospheres. The reaction temperatures range from about -20 to+150 C., prefereably 0 to 100 C. One variant of the amidation resides inconverting an acid of formula I (R, COOH) first with a chloroformic acidester of the formula ClCOOA in the presence of a base, e.g.,triethylamine, into the mixed anhydride of the formula Z- CHR- COO-COOA,and then further reacting the latter with the amine.

Amides of Formula I (R, CONH can optionally be dehydrated to thenitriles of Formula I (R, CN), for example with a dehydration agent,e.g., P 0 POCl p-toluenesulfochloride/pyridine, at temperatures of about0 to 200 C., preferably 20 to 100 C. Heating of the carboxylic acids ofFormula I (R, COOH) with lower alkanoic acid anhydrides produce the acidanhydrides of Formula I (R, --COO-- CO-CHR,-Z).

Aldehydes of Formula I (R, Cl-IO) optionally can be converted intohemiacetals, e.g., those of the formula Z-CI-IR CHCI-IOA, or acetals,e.g., those of the formula ZCHOH2CH(OA) by treatment with an acetalizingagent, e.g., an alcohol. For example, the aldehyde is reacted with analcohol of the formula AOI-I, e.g., methanol, ethanol, n-propanol,isopropanol, n-butanol, isobtuanol, or with a glycol of the formulaHO-C,,,I-I ,,,OH wherein m 2, 3 or 4 e.g., ethylene glycol,1,2-propanediol, 1,3-propanediol, 1,2- butanediol, 2,3-butanediol,1,4-butanediol, or with a phenol of the formula ArOH, with the additionof a reaction catalyst. The condensation of the aldehydes withpolyhydric alcohols or phenols produces cyclic acetals. For example,with 1,2-glycols, derivatives of 1,3- dioxolane are obtained and with1,3-glycols, derivatives of 1,3-dioxane are produced. Suitable catalystsare acids, e.g., mineral acids, e.g., HCl, H H PO sulfonic acids, e.g.,p-toluene-sulfonic acid Also suitable, for example, are NaI-ICO P 0 CaClFeCl ZnCl iodine, anhydrous CuSO, and cation exchangers. The water ofreaction advantageously is removed by azeotropic distillation using anentraining agent, e.g., benzene, toluene, pertroleum ether. Anadvantageous mode of operation for producing the dimethylordiethylacetals is introducing gaseous hydrogen chloride (approximatelyup to 1%) into the methanolic or ethanolic solution of the aldehyde.

Acetals of the formula ZCHR CI-I(OA) can also be produced by reactingthe aldehydes with orthoformic acid esters of the formula I-IC(OA) inthe presnece of an acidic catalyst. In general, these substances arepermitted to react in the corresponding alcohol of the formula A-OI-I.The catalysts are suitably small amounts of a mineral acid, aromaticsulfonic acid, FeCl NH CI, NI-I NO KHSO, or a hydrochloride of a base,e.g., pyridine hydrochloride. Advantageously, the reaction mixture isbriefly heated and then allowed to stand for some time at roomtemperature. In place of the orthoformic acid esters, it is alsopossible to employ formimido ester salts, e.g., formimido esterhydrochlorides. The reaction of the aldehydes with orthosilicic acidesters of the formula Si(OA) in an alcoholic solution in the presence ofacids or acidreacting substances likewise results in the desiredacetals. Furthermore, a combination of an alcohol of the formula A-OI-Iwith dimethyl sulfite in the presence of an acidic catalyst can likewisebe used for the acetalization. During the reaction, S is liberated sothat the progression of the reaction can be followed by observing thegas evolution.

A further method for the production of acetals is thetrans-acetalization of a lower acetal, e.g., dimethylor diethylacetal,in the presence of an acidic catalyst and a higherboiling alcohol, e.g.,a glycol of the formula I-IO-C,,,I-I ,,,OH, wherein m is an integer from2 to 6. The thus-obtained equilibrium can be shifted by removing thelower alcohol in favor of the acetal of the higher-boiling alcohol. Foraccomplishing the reaction, it is sufficient to reflux the lower acetalfor some time with an excess of the higher-boiling alcohol with theaddition of an acidic catalyst, e.g., HCI, H 80 p-toluenesulfonic acid,FeCl or BF Dihydric and polyhydric alcohols react particularly smoothlywith lower acetals, so that this process is especially well suitable forthe preparation of cyclic acetals. It is also possible to combine theproduction of the acetal with orthoformic acid esters and thetrans-acetalization into one operation. Under the conditions oftrans-acetalization, an exchange of the carbonyl compounds can likewiseoccur. Thus, an aldehyde of Formula I (R, CHO) can be converted, e.g.,with acetone dimethyl ketal or butanone ethylene ketal, in the presenceof p-toluenesulfonic acid, into the corresponding dimethylorethyleneacetal. The thus-liberated acetone or butanone, respectively, isremoved from the equilibrium.

I-Iemithioacetals, e.g., those of the formula ZCI-I- R -CHOASA, orthioacetals, e.g., those of the formula ZCHR CH(SA) are obtained byreacting the aldehydes of Formula I (R, CHO) with mercaptoalkanols,e.g., those of the formula HSC,,,H ,,,OH wherein m has the values givenabove, preferably 2-mercaptoethanol, mercaptans, e.g., those of theformula A-SH, preferably methylor ethylmercaptan, or N-propyl-,isopropyl-, n-butyl-, isobutyl-, n-amyl-, nhexyl-, n-heptyl,n-octylmercaptan, or dithiols, e.g., those of the formula HSC,,.I-I SI-Iwherein in has the values given above, preferably ethane-1,2-dithiol, orpropane-l,2,-dithiol, propane-l,3,-dithiol, butanel,2-dithiol,butane-2,3-dithiol, butane-1,4-dithiol. In the foregoing description andin the following description, the mercaptoalkanols, mercaptans, anddithiols are included within the term acetalizing agents. Thecondensation of the aldehydes with these substances takes place rapidlyat room temperature. In general, a temperature of 70 to +200 C. issuitable for the reaction. The reaction can be conducted, especiallywith low-boiling mercaptans, in the presence of an inert solvent, e.g.,a hydrocarbon, e.g., benzene, toluene or xylene. Apreferred catalyst isboron trifluoride etherate, with or without the addition of acetic acid.

Aldehydes of Formula I (R CHO) can also be converted into thecorresponding acylates, e.g., those of the formula Z-CHR --CI-I(OAc) bytreatment with an acy ating agent, e.g., an acid anhydride. At anelevated temperature and in the presence of an acidic catalyst, onemolar equivalent of l-I-OAc can be eliminated from the acylates, withthe formation of the corresponding enol acylates, e.g., of the formulaZ-CR =CI-I-OAc.

The free aldehydes of Formulal (R CI-IO) can also be converted, byreaction with a metal bisulfite solution, into stable, often crystallineaddition compounds of the formula Z-CI-IR -CHOI-I-SO M (M 1 preferablyNa). In general, this reaction is carried out by dissolving the freealdehyde in ether and treating the solution with a concentrated aqueousNal-ISO solution. It is sometimes advantageous to employ an alcohol,e.g., methanol or ethanol, as an additional solvent, or to add thisalcohol to achieve quantitative precipitation toward the end of thereaction. The bisulfite solution can be freshly prepared by combining 1mole of Na SO and 1 mole of acetic acid. Another mode of operation is tocombine the aldehyde and an aqueous Na solution, introduce S0 andcontinuously neutralize the thus-liberated sodium hydroxide solution.Also, S0 can convert aqueous aldehyde solutions or suspensions intobisulfite compounds by the continuous addition of NaOI-I. The bisulfitecompounds are, in most cases, difficult to dissolve in excess NaI-ISOsolution. They can therefore be easily separated therefrom and cannormally be purified by recrystallization from aqueous ethanol.

The aldehydes of Formula I (R, CI-IO) can also be converted into otherfunctional derivatives in accordance with methods described in theliterature, e. g., oximes, semicarbazones, phenylhydrazones andsubstituted phenylhydrazones.

Ethers of Formula I (R etherified CH OH-group, preferably CI-I OA) areobtained from alcohols of Formula I (R Cl-l OH) by reacting thecorresponding alkali metal alcoholates with an alkyl halogenide, alkylmethanesulfonate or alkyl p-toluenesulfonate. The alkali metalalcoholates are obtained by agitating the alcohol of Formula I (R CHOI-I) in an inert solvent, e.g., ether, THF, dioxane, or benzene, withfinely divided Na, NaNI-I or NaH until the evolution of hydrogen orammonia, respectively, is terminated. Thereafter, the alkyl halogenide,most advantageously the respective alkyl iodide, is added thereto andthe mixture refluxed for several hours.

Ethers of Formula I (R etherified CI-I OI i-group) are also produced byreacting alcohols of Formula I (R CI-I OH) in an inert solvent, e.g.,ether, benzene or toluene, with a diazoalkane, by the addition ofcatalytic amounts of a Lewis acid, e.g., AlCl BF or FeCl The amount ofcatalyst added is normally dependent on the reaction velocity, i.e.,reactions which are slowing down can be accelerated by the addition offurther amounts of the catalyst.

Finally, alcohols of Formulal (R CH OI'I) can also be converted into thecorresponding ethers by adding these alcohols to olefins. Preferredolefins are those hydrocarbons produced by splitting off water from atertiary alcohol. The addition step is executed in the presence of anacidic catalyst, e.g., mineral acids, tetrafluoroboric acid, perchloricacid, or BF In some cases, basic catalysts are also suitable, e.g.,alkali metal alcoholates. An excess of the olefin is a suitable solventbut normally inert solvents are employed, e.g., THF,

dioxane, benzene or toluene. The preferred reaction temperature is theboiling temperature of the selected solvent. Thus, for example, it ispossible to obtain the 2-(2-dibenzofuryl)-propyl-tert.-amyl ether from2-(2- dibenzofuryl)-propanol and trimethylethylene.

Functional derivatives of compounds of Formula I (e.g., R functionallymodified COOH or Cl-l OH- group) can be converted, by furthermodifications, into other functional derivatives of the same type. Forexample, esters containing additional reactive groups in the alcoholportion can be converted into other esters. For example, haloalkylesters (e.g., 2-chloroethyl esters) of acids of Formula 1 (R COOl-l) canbe reacted with sodium alcoholates to alkoxyalkyl esters or withdialkylamines to dialkylaminoalkyl esters, suitably in the presence ofan inert solvent, e.g., benzene or chloroform, at temperatures of fromto 150 C., preferably 20 and 100 C., optionally also under elevatedpressure.

It is also possible to convert, in a thus-obtained product of Formula I,an R group, preferably an optionally functionally modified COOH orCll-lO-group, by treatment with reducing agents, into another R group,preferably an optionally functionally modified CHO or CH Ol-l-group.

Suitable for such reductions are, e.g., compounds of Formula I wherein Ris COOI-l, COCl, CN, -COOA, -CO-SA, CON(A) CHO, COHal, COOAc, CO-OCOCHR-Z, CON or Cl-l(OA) For example, aldehydes of the formula ZCHR CHO areobtainable from acid chlorides Z-Cl-l- R --COCl by catalytichydrogenation according to the Rosenmund method (suitably under normalpressure using a Pd/BaSQ, catalyst in benzene, toluene or xylene as thesolvent; or by reaction with quinoline and NaCN according to theReissert method; or by reaction with a lithium tri-tert.-alkoxyaluminumhydride, e.g., lithium tri-tert.-butoxyaluminum hydride; or fromnitriles ZCl-lR -CN by reduction with SnCl /HCl according to the Stephenmethod; or reduction with a dialkylaluminum hydride, e.g.,diisobutylaluminum hydride. These aldehydes are also obtainable fromesters of the formula Z-CHR -COOA by reaction with dialkylalmuminumhydrides or lithium tri-tert.-alkoxyaluminum hydrides; and fromunsaturated esters of the type Z- C(=R)-COOA, e.g.,2-(2-dibenzofuryl)-acrylic acid ethyl ester; or from acid imidazolidesor 3,5- dimethylpyrazolides or carbazolides, e.g., N-[2-(2-dibenzofuryl)-propionyl]imidazole or 3,5- dimethylpyrazole or carbazole,or from acid aziridides of the formula /CH CH Z-CHR CON agents of allkinds, e.g., pulverized iron in aqueous acetic acid. LiAl1 NaBH aluminumalcoholates, such as aluminum isopropylate, according to the method ofMeerwein-Ponndorf, e.g., in benzene or to]- uene at temperatures ofbetween about 20 and about 1 10 C.; from acid azides of the formulaZCl-l- R CON by reaction with NaBl-l from acid chlorides of the formulaZCHR -COCl by reaction with NaAll-L, or LiAll-l from acid amides of theformula ZCHR -CONH by reaction with alkali metals in lower alcohols,e.g., Na in ethanol; and from mixed carbonic acid esters of the fomulaZ-CHR- COO-COOA by reaction with LiAlH Ethers of the fomula ZCHR -CH OAare obtainable, for example, by reduction of the corresponding esters ofthe formula Z-Cl-lR COOA with diborane, which can be produced in situfrom NaBl-l /BF or LiAll-l /BF Further details of the reducing methodsare described above, e.g., paragraph (c).

Ethers or esters of the formula ZCHR CH OR wherein R is a group whichcan be split off by hydrogenolysis, e.g., benzyl, diphenylmethyl,triphenylmethyl, p-methylbenzyl, 2-picolyl or carbobenzoxy, can be splitreductively, thus forming alcohols of Formula l (R, CH OH). A preferredhydrogenolysis is conducted with hydrogen in the presence of a Pdcatalyst, e.g., Pd on charcoal. Thus 2-(2-dibenzofuryl)- propanol isobtained, for example, from 2-(2- dibenzofuryl)-propylbenzyl ether.

Conversely, it is also possible, in a thus-obtained compound of FormulaI, to oxidize an R, group, especially a CH OH or CHO-group, to another Rgroup, especially a CHO- or COOH group.

Alcohols of the formula Z--CHR --Cl-l OH and aldehydes of the formulaZCl-IR CHO can readily be converted into the corresponding carboxylicacids of the formula ZCl-lR COOl-l with a plurality of oxidizing agents.These oxidizing agents include chromic acid and/or the salts thereof,e.g., sodium dichromate, preferably in an aqueous-sulfuric acid mediumand/or with the addition of acetone, acetic acid and/or benzene as thesolvent; silver oxide, which can suitably be prepared in situ fromsilver nitrate and NaOH, preferably in an aqueousalkaline medium;KMnO,,, for example, in pyridine; NiO for example, in THF in thepresence of a base, e.g., Na CO An oxidation of alcohols of the formulaZ-CH- R CH OI-l to the corresponding aldehydes is likewise possible,which can be accomplished according to methods described in detail inthe literature. For example, these alcohols can be dehydrogenatedcatalytically with hydrogen being split off, or with the aid ofoxidation agents.

The catalytic dehydrogenation is suitably effected under reducedpressure in the vapor phase. Suitable catalysts are primarily copper,silver and zinc compounds. The reaction temperature is normally betweenl00 and 450 C. The dehydrogenation can also be conducted in the presenceof hydrogen acceptors. Suitable as such acceptors are, above all,aromatic nitro compounds, e.g., nitrobenzene or m-dinitrobenzene. Asuitable catalyst is pulverized copper, for example. The reaction isconducted by heating the reactants in an inert solvent, e.g., xylene,while passing air through the reaction mixture.

The oxidation can furthermore be conducted, for example, with chromicacid. The reaction can be effected in an aqueous solution or anotherinert solvent at a temperature of from to l00 C. Also the chromicacid-pyridine complex is suitable as an oxidation agent. Nitrogen orcarbon dioxide can be introduced into the reaction mixture in order tosuppress the further oxidation of the thus-formed aldehyde. A variant ofthe CrO oxidation is the dehydrogenation with tert.-butyl chromate whichis conducted in excess tert.-butanol or in an inert diluent, e.g.,petroleum ether, benzene or CCl,.

Further oxidation agents for the oxidation of the alcohols of Formula l(R, CH OH) to the aldehydes of Formula 1 (R CHO) are MaO which is usedin dilute sulfuric acid but can also be employed suspended in inertorganic solvents, e.g., petroleum ether or acetonitrile; PbO leadtetraacetate, which is used in acetic acid or also in benzene,optionally with the addition of some pyridine; SeO N 0 mostadvantageously in CHCl or CCl N-haloamides, e.g., N- bromosuccinimide,which compounds can be employed in acetic acid/sodium acetate or inpyridine; concentrated HNO or m-nitrobenzenesulfonic acid; or l-chlorobenzotriazole.

With the use of very low-volatile carbonyl compounds as hydrogenacceptors, e.g., diphenylcarbaldehyde, benzoquinone orphenanthrenequinone, it is also possible to convert alcohols of theformula Z-CI-l- R Cl-l OH into the aldehydes according to the Oppenauermethod. In this reaction, the alcohol is first converted into thealcoholate with the stoichiometric amount of aluminum isopropylate oraluminum phenoxide, and then mixed with an excess of the highboilinghydrogen acceptor. The thus-formed aldehyde can be distilled fromtheredox equilibrium, for exam ple, under reduced pressure.

Anodic oxidation can likewise be utilized for the dehydrogenation ofalcohols of Formula I (R CH OH).

A preferred oxidation method resides in converting alcohols of theformula Z-CHR -CH- ,OH into the aldehydes of Formula l (R, CHO) withdimethyl sulfoxide (DMSO). This reaction is advantageously carried outin the presence of an agent splitting off water, e.g., acetic anhydrideor, in an even gentler manner, in the presence ofdicyclohexylcarbodiimide with the addition of a suitable acid, e.g.,trifluoroacetic acid or H PO by allowing the components to react witheach other at temperatures of from 0 to 50 C., preferably at about roomtemperature, for about 0.5 24 hours.

In a thus-obtained product of Formula I, an R group can be convertedinto another R group by substitution reactions and/or furtherconversions of the introduced or already present substituents.

For example, it is possible to introduce, by halogenation, alkylation,nitration, etc., a halogen atom, an al-- kyl, alkanoyl, monoalkylamino,dialkylamino, acylamino, amino, or nitro group into the dibenzofuranand/or the dibenzothiophene ring. An amino group can be diazotized andthe thusobtained diazonium residue can be further converted into otherfunctional groups.

Thus, according to methods described in the litera ture, one of thefollowing substituents can be introduced into the dibenzofuran ordibenzothiophene ring, respectively:

a. Chlorine:

For example, by direct reaction with elemental chlorine in an inertsolvent, such as water, aqueous sodium hydroxide solution, ether,tetrachloromethane, acetic acid, without or with the addition ofspecific catalysts, such as, for example, FeCl AlCl 3, SbCl or SnCl,,preferably between l 0 and 100 C., or by reaction in a stronglyhydrochloric solution with H 0 or with Na- C10 wherein the chlorinationis effected by the chlorine produced in the nascent state, or byreaction with SO CI in an inert solvent, such as chlorobenzene, in thepresence of radical-forming catalysts, e.g., peroxides, at preferably l80 C.

b. Bromine:

For example, by direct reaction with elemental bromine in an inertsolvent, such as water, aqueous sodium hydroxide solution, carbondisulfide, acetic acid, chloroform, tetrachloromethane, or dioxane,especially with the addition of catalysts effective as brominetransferagents, such as iron filings, AlCl AlBr FeCl iodine, or pyridine,preferably between -30 and C., or by reaction with hypobromous acid,acylhypobromites, N-bromoimides, such as N- bromosuccinimide,N-bromophthalimde, or other bromine-yielding agents, such asl,3-dibromo-5,5- dimethylhydantoin, in inert solvents, such asnitrobenzene or carbon disulfide, preferably at l0 to 150 C.

c. Iodine:

For example, by direct reaction with elemental iodine, especially in thepresence of nitric acid in chloroform or of HgO in an inert solvent,such as alcohol, acetic acid, or benzene, preferably at temperatures ofbetween 0 and 120 C., or by reaction with iodine alkali metal iodidesolutions in the presence of carbonates, acetates, alkali metalhydroxide solutions, ammonia, or amines, or by reaction of mixtures ofalkali metal iodides and oxidation agents, such as alkali metal iodates,alkali metal nitrates, or H 0 in inert solvents, such as water, aceticacid, or ethanol, wherein the thusliberated iodine reacts in the nascentstate, or by reaction with Cll in dilute acetic acid, preferably at 50C., or after mercuration, for example in an aqueous or acetic mediumwith mercury(II) acetate to the HgOCOCl-I compound and exchange of theorga nometallic residue against iodine, for example by reaction withiodine or iodine alkali metal hydroxide solu tions.

d. Nitro:

For example, with the aid of the following agents: a mixture ofanhydrous nitric acid with BF metal nitrates, such as Cu, Fe, Mn, Co, Ninitrate, in a mixture with acetic acid or acetic anhydride; metalnitrates, such as Ag, Ba, Na, K, NH or Pb nitrate, in a mixture withFriedel-Crafts catalysts, such as AlCl FeCl BF or SiCl alkyl nitrates,such as ethyl nitrate, in a mixture with concentrated sulfuric acid, HBFor Lewis acids, such as BCl SnCl PCl AlCl SiCl SbCl or Fecl nitrylfluoride, chloride, bromide, perchlorate, or tetrafluoroborate,preferably in the presence of Friedel-Crafts catalysts, such as AlClFeCl ZrCl,,, or AlBr in solvents such as carbon disulfide, n-pentane, orCHCl nitrogen oxides, such as N 0 N 0 in the presence of concentrated H80 HF, or Friedel-Crafts catalysts, such as B1 AlCl or FeCl optionallyin solvents, such as tetramethylenesulfone or acetic acid; concentratednitric acid" mixtures of concentrated sul-

1. A COMPOUND OF THE FORMULA
 2. A compound of claim 1, wherein R1 isCOOR6 in which R6 is H, alkyl of 1-8 carbon atoms or dialkylaminoalkylof up to 10 carbon atoms.
 3. A compound of claim 1, wherein R1 is COOH,COOCH3 or COOC2H5.
 4. A compound of claim 1, wherein R2 is CH3 or C2H5.5. A compound of claim 4, wherein R2 is CH3.
 6. A compound of claim 1,wherein R3 is H, CH3, C2H5, CH3O, CH3CO, F, Cl, Br, I, OH, NH2 or NO2.7. A compound of claim 6, wherein R3 is H.
 8. A compound of claim 1,wherein R1 is COOH or COOAlkyl wherein alkyl is of 1-8 carbon atoms, R2is CH3 and R3 is H, C2H5, F, Cl, Br or I.
 9. A compound of claim 8,wherein R3 is H or F.
 10. A compound of claim 8, wherein R3 is H or 7-F.11. A compound of claim 1, 2-(2-dibenzofuryl)-propionic acid.
 12. Acompound of claim 1, the ethyl ester of 2-(2-dibenzofuryl)-propionicacid.
 13. A compound of claim 1, the 2-diethylaminoethyl ester of2-(2-dibenzofuryl)-propionic acid.
 14. A compound of claim 1, the2-(2-dibenzofuryl)-butyric acid.
 15. A compound of claim 1, the2-(2-dibenzothienyl)-propionic acid.
 16. A compound of claim 1, theethyl ester of 2-(2-dibenzothienyl)-propionic acid.
 17. A compound ofclaim 1, the 2-diethylaminoethyl ester of 2-(2-dibenzothienyl)-propionicacid.
 18. A compound of claim 1, the2-(8-ethyl-2-dibenzofuryl)-propionic acid.
 19. A compound of claim 1,the ethyl ester of 2-(8-ethyl-2-dibenzofuryl)-propionic acid.
 20. Acompound of claim 1, the 2-(7-fluoro-2-dibenzofuryl)-propionic acid. 21.A compound of claim 1, the ethyl ester of2-(7-fluoro-2-dibenzofuryl)-propionic acid.
 22. A compound of claim 1,the 2-(8-fluoro-2-dibenzofuryl)-propionic acid.
 23. A compound of claim1, the 2-(7-chloro-2-dibenzofuryl)-propionic acid.
 24. A compound ofclaim 1, the 2-(8-bromo-2-dibenzofuryl)-propionic acid.
 25. A compoundof claim 1, the ethyl ester of 2-(8-bromo-2-dibenzofuryl)-propionicacid.
 26. A compound of claim 1, the 2-(8-iodo-2-dibenzofuryl)-propionicacid.
 27. A compound of claim 1, the 4-carbethoxycyclohexyl-ammoniumsalt of 2-(2-dibenzofuryl)-propionic acid.